Fallopian tube tumors: an overview

Identity

ICD-Topo	C570 Fallopian tube
Atlas_Id	5279
Phylum	Female organs: Fallopian tube::Fallopian tube tumor
WHO/OMS Classification	Female organs
Note	Introduction This article shall give an overview of different tumors occurring in the fallopian tube. Though being a very rare location of primary or exclusive tumor manifestation, the fallopian tube is now receiving increased attention in gynecological oncology since considerable evidence suggests that it represents the site-of-origin of many (if not most) serous pelvic carcinomas (Folkins et al., 2009; Dietl and Wischhusen, 2011; Dietl et al., 2011; Seidman et al., 2011; Vang et al., 2013). Disease definition A tumor is classified as primary fallopian tube tumor when it is either restricted to this anatomical structure, or when the fallopian tube is most affected whereas co-locations such as ovary and uterus show lesser involvement or a different histology (Alvarado-Cabrero et al., 2003; Folkins et al., 2009). As recent data indicate that the fallopian tube is the site-of-origin of serous pelvic carcinomas (Folkins et al., 2009; Dietl and Wischhusen, 2011; Dietl et al., 2011; Seidman et al., 2011; Vang et al., 2013), histological assessment of the respective involvement of ovaries and fallopian tubes may not be sufficient to distinguish between advanced stages of fallopian tube and ovarian carcinomas (Kosary and Trimble, 2002). Inevitably, the considerable overlap between ovarian and fallopian tube carcinomas warrants some coverage of ovarian cancer in this context. Nevertheless, as ovarian carcinomas constitute a well-accepted clinical entity (irrespective of their potential origin from the fallopian tube) they shall largely be dealt with in a separate place.
	Figure 1: WHO Classification of solid tumors of the fallopian tube (Alvarado-Cabrero et al., 2003).

Classification

Note	Solid fallopian tube tumors can be subcategorized based on origin and behavior. The WHO classification distinguishes several groups of solid tumors of the fallopian tube (Alvarado-Cabrero et al., 2003) shown in Figure 1.
Note	Table 1: TNM and FIGO Classification of carcinomas of the fallopian tube (UICC, 2009). Table 2: Staging of fallopian tube carcinomas (UICC, 2009).
	Staging Malignant tumors of the fallopian tube are classified according to the "Union International contre le cancer" (UICC) and the "Fédération internationale de Gynécologie et d'Obstétrique" (FIGO, Table 1 and 2). The TNM classification is based on clinical and pathological findings whereas the FIGO classification requires a surgical staging (UICC, 2009; AJCC, 2010). According to the TNM classification, the carcinomas of the fallopian tube approximate different stages (Table 2).

Clinics and Pathology

Etiology	The etiology of primary fallopian tube tumors is unknown. Multiparity seems to be protective (Riska et al., 2003), pregnancies and oral contraceptives decrease the risk (Inal et al., 2004). Neither age, nor weight, education level, pelvic inflammatory disease, infertility, previous hysterectomy or endometriosis show significant correlations especially with fallopian tube carcinomas (Henderson et al., 1977; Demopoulos et al., 2001; Inal et al., 2004). Demographic distribution is similar to ovarian cancer, and the highest incidence was found in white, non-Hispanic women and women aged 60-79. However, recent evidence suggests tubal cancer to be much more frequent (Stewart et al., 2007; Piek et al., 2008).
Epidemiology	Epidemiological data on malignant fallopian tube tumors are adequate, even though only 0.3-1.1% of all gynecological malignancies are typically classified as primary fallopian tube carcinomas (Baekelandt et al., 2000), mostly adenocarcinomas (Schneider et al., 2000). In the U.S., the incidence is about 3.6 per million women per year (Rosenblatt et al., 1989). Stage-adjusted survival rates are generally better than for epithelial ovarian carcinoma (Kosary and Trimble, 2002). Underestimation of the real incidence might be due to fallopian tube carcinomas being mistaken for ovarian cancers (Woolas et al., 1994) which show a significantly higher prevalence. Still, Riska and colleagues reported an increasing incidence of fallopian tube carcinomas from 1.2 per million per year for 1953-1957 to 5.4 per million per year from 1993-1997 (Riska et al., 2003).
Clinics	Clinical presentation Patients with benign tumors of the fallopian tube are often asymptomatic or report local pain. The tumors are incidentally found during operations for other indications (Etoh et al., 2012). Benign tumors can abet tubal torsions (Alvarado-Cabrero et al., 2003). Especially papillomas can obstruct the fallopian tube (Gisser, 1986). Obstruction of the fallopian tube can cause infertility (Heller et al., 1991; Heatley, 2001). Primary fallopian tube carcinomas most frequently occur between the fourth and sixth decade of life with a mean patient age of 55 years (Boutselis and Thompson, 1971; Sedlis, 1978). Stewart et al. found an incidence rate of 0.41 per 100000 women with highest incidence rates in women aged 65-69 in a study including 3051 cases of primary fallopian tube carcinomas (Stewart et al., 2007). Symptoms are very diffuse, the Latzko triad of symptoms - intermittent profuse serosanginous vaginal discharge, colicky pain relieved by discharge, abdominal or pelvic mass - is reported in only 15% of all patients (Ajithkumar et al., 2005). 5% of the patients show a hydrops tubae profluens. Fallopian tube carcinomas are diagnosed at earlier stages than epithelial ovarian cancers (Peters et al., 1988; Rose et al., 1990; Gadducci et al., 2001; Pectasides et al., 2006). 10-36% show positive PAP smear tests with intermittent detection of abnormal, suspicious or poorly differentiated cells or glands (Ajithkumar et al., 2005). In 80% of the advanced stages, peritoneal metastases occur (Levite et al., 2001). Also haematogenous or transluminal metastases were found (Yoonessi, 1979). Bilateral tubal involvement has been described in 10-27% of fallopian tube carcinomas (Schiller and Silverberg, 1971; Hirai et al., 1989; Rose et al., 1990; Alvarado-Cabrero et al., 1999; Rosen et al., 1999; Gadducci et al., 2001). The higher rate of lymph node metastases in comparison to ovarian cancer should be considered, as staging of fallopian tube carcinomas is surgical. Compared to epithelial ovarian cancer, fallopian tube carcinomas show a higher rate of retroperitoneal and distant metastases (Yoonessi, 1979; McMurray et al., 1986; Maxson et al., 1987; Asmussen et al., 1988; Peters et al., 1988; Gadducci et al., 2001). Para-aortic lymph node metastases were detected in 33% of patients (Tamimi and Figge, 1981). Another study revealed 42-59% lymph node metastases in routine lymphonodectomy with equal involvement of para-aortic and pelvic lymph nodes (Ajithkumar et al., 2005). If routine lymphonodectomy is not performed, a surgical understaging may occur. Overall, 20-25% of patients with fallopian tube carcinomas showed FIGO stage I, 20% stage II, 45-50% stage III and 5-10% stage IV (Ajithkumar et al., 2005). Ectopic β-HCG-production was reported in two cases of serous or undifferentiated fallopian tube carcinomas (Carapeto et al., 1978; Alvarado-Cabrero et al., 1999). These tumors contained syncytiotrophoblast-like cells. Case reports about renin-producing or alpha fetoprotein (AFP)-producing tumors have been published (Aoyama al., 1996; Zabernigg et al., 1997). Fallopian tube carcinomas show frequent expression of CA-125 (Puls et al., 1993). Hence, >80% of the patients show elevated CA-125 serum levels (McMurray et al., 1986; Ajithkumar et al., 2005) that correlate significantly with disease-free and overall survival (Rosen et al., 1999; Ajithkumar et al., 2005). Adenomyomas can also cause elevated CA-125 levels and small volumes of serous ascites. With some limitations, CA-125 may thus be considered as suitable tumor marker for use in cancers of the fallopian tube (Baekelandt et al., 2000). The average lead time of increasing CA-125 levels versus clinical or radiological diagnosis of recurrence is three months with a range from 0.5 to 7 months (Ajithkumar et al., 2005). Fallopian tube carcinomas can cause paraneoplastic symptoms. For example, a paraneoplastic cerebellar degeneration (PCD) with Anti-Yo antibodies is associated with fallopian tube carcinomas (Levite et al., 2001; Tanaka et al., 2005; Selby et al., 2011).
	Figure 2: Histology of an invasive serous-papillary adenocarcinoma of the fallopian tube. a: Tumor formation in the tubal wall. b shows 200 fold magnification with gland formation (*). c: Metastasis in adipous tissue. d: Immunohistochemistry for Ki67 with nuclear positivity. e and f: Immunohistochemistry for p53 also with nuclear positivity. Figure 3: a: In this H&E staining, the STIC cells show polymorphic nuclei and a multilayer epithelium (arrowheads) compared with normal tubal epithelium (arrows). b: Distinct transition from normal tubal epithelium to p53 positive STIC (p53 immunohistochemistry). c: Invasive fallopian tube carcinoma (arrowheads) next to STIC formation (arrows, H&E).
Pathology	Benign tumors Benign tumors are often solid and clearly delimited. They arise at the intraluminal or serosal surface of the fallopian tube. Papillomas show fibrovascular stacks with epithelial lining. They can obstruct the fallopian tube (Gisser, 1986). Adenofibromas and cystadenofibromas occur between the third and eighth decade. They remain asymptomatic and are diagnosed incidentally during other operations (Zheng et al., 1996). Macroscopically, these tumors grow to 0.5-3cm and can be intraluminal or at the serosa surface as well as at the fimbriae. They show a stromal and a papillary structured fraction (Alvarado-Cabrero et al., 2003). In fallopian tubes resected post partum, few metaplastic papillary tumors were detected (Saffos et al., 1980; Keeney and Thrasher, 1988; Bartnik et al., 1989). These tumors consist of papillae lined by epithelium displaying patterns of a serous borderline tumor. The cells can be positive for intracellular mucin (Alvarado-Cabrero et al., 2003). Adenomyomas consist of bundle-like growing leiomyoma cells and sometimes endometrial tissue remnants. Endometrioid polyps occur in the interstitial part of the tube attached to the intratubal epithelium and sometimes cause infertility (Heller et al., 1991; Heatley, 2001). Cystadenofibromas can show vimentin-cytokeratin-coexpression. Further, diffuse apical epithelial membrane antigen (EMA) immunoreactivity occurs. Gürbüz et al. suggest that tumors are derived from embryonic remnants of the Müllerian duct (Gürbüz and Ozkara, 2003). Borderline tumors of the fallopian tube occur very rarely and can show serous, mucinous or endometrioid differentiations. Histological features resemble those in borderline tumors of the ovary (Alvarado-Cabrero et al., 1997). Mucinous tumors of the fallopian tube can be associated with pseudomyxoma peritonei (McCarthy and Aga, 1988), other mucinous lesions or Peutz-Jeghers-Syndrome (Seidman, 1994). There are also reports about adenofibroma with borderline malignancy. The prognosis seems to be favorable (Zheng et al., 1996; Alvarado-Cabrero et al., 1997). Precursor lesions: Intraepithelial carcinoma Non-invasive carcinomas of the fallopian tube were formerly known as "carcinoma in situ". This term should be abandoned as it implies restricted local tumor formation. Intraepithelial carcinoma cells can, however, form implants on the ovarian surface and the peritoneum. Recent publications highlight the fallopian tube as likely site-of-origin of primary pelvic serous carcinomas detected in the fallopian tube, the ovary or the peritoneum (Folkins et al., 2009; Dietl and Wischhusen, 2011; Dietl et al., 2011; Seidman et al., 2011; Vang et al., 2013). Serous tubal intraepithelial carcinomas (STIC) as well as endometrioid intraepithelial carcinomas (EIC) are thus considered as precursor lesions (Ambros et al., 1995; Carlson et al., 2008). This hypothesis is supported by findings from Colgan et al. who found a high frequency of pre-cancerous lesions in fallopian tubes from patients with BRCA gene mutations (Colgan, 2003). Lee and colleagues could detect mutant p53-signatures predominantly in epithelial cells at the fimbriated ends of fallopian tubes from patients with BRCA1 and 2 mutations. Moreover, the same signatures were also found in corresponding ovarian cancer tissues (Lee et al., 2007). Interestingly, Li-Fraumeni-Syndrome - which is associated with p53 mutations and generally increased risk for serous carcinomas - does not correlate with a higher incidence of PPSC, especially fallopian tube carcinomas. Thus, it seems that other mutations e.g. those affecting BRCA are required to drive PPSC development (Xian et al., 2010). Kim and colleagues could prove by histology that serous epithelial cancers develop in the fallopian tubes of Dicer-PTEN-double-knockout mice. By histology and pathological behavior these tumors showed characteristic traits of serous epithelial ovarian cancer, even though oophorectomy was not protective. Instead, tumor development could be prevented by salpingectomy (Kim et al., 2012). Furthermore, in prophylactic salpingo-oophorectomy specimen, occult carcinomas are more frequent in the fallopian tube than the ovary (Vang, 2011). While carrying the potential of invasiveness, the STIC cells grow sparing the tubal stroma. Figure 3 focusses on the STIC with its distinct cellular alterations such as polymorphic nuclei, multilayer epithelium and atypic mitoses. Figure 3d also shows an invasive fallopian tube carcinoma with an adjoining STIC. In clinical studies, a frequent coexistence of pelvic serous carcinoma and tubal intraepithelial carcinomas was found in unselected (Przybycin et al., 2010) and BRCA mutated patients (Kindelberger et al., 2007). Shortening of telomeres is another early event in PPSC development and already detectable in the STIC (Kuhn et al., 2010). As the post-reproductive fallopian tube lacks physiological functions and also causes complications such as hydrosalpinx, Dietl et al. suggested combined hysterosalpingectomy instead of simple hystercectomy or salpingectomy as a recommendable method for sterilization in clinical routine (Dietl and Wischhusen, 2011; Dietl et al., 2011). Invasive carcinoma All tumor subtypes in the ovaries are also known in the fallopian tube, with serous carcinomas being most frequent. In a series of 105 fallopian tube carcinomas Alvarado-Cabrero et al. found the following distribution of different histologies: About 50% were serous, 25% endometrioid, 20% transitional cell or undifferentiated carcinomas and 5% were of other subtypes (Alvarado-Cabrero et al., 1999). Serous adenocarcinomas are generally invasive with 50% G3 tumors (Alvarado-Cabrero et al., 1999). Sometimes immune cell invasion disguises the tumor as salpingitis (Cheung et al., 1994). Mucinous adenocarcinomas, a very rare entity, are often associated with other mucinous carcinomas of the female genital tract or the appendix (Seidman, 1994). Endometrioid adenocarcinomas are very often non-invasive or superficially invasive and show a favorable prognosis (Navani et al., 1996). A part of those tumors displays characteristics of the wolffian adnexal tumor (Daya et al., 1992; Navani et al., 1996). Clear cell adenocarcinomas account for 2-10% of all fallopian tube carcinomas (Voet and Lifshitz, 1982; Hellstrom et al., 1994; Alvarado-Cabrero et al., 1999). Transitional cell carcinomas are rare in the genital tract. Still, the frequency between 11 and 43% of all fallopian tube carcinomas makes it an important locus-specific entity (Uehira et al., 1993; Alvarado-Cabrerog et al., 1999). Undifferentiated carcinomas lack any patterns of squamous cells or glandular cells but instead contain multinuclear giant cells (Alvarado-Cabrero et al., 1999). Lacy et al. reported immunohistochemical positivity for c-erbB-2 (HER-2/neu) overexpression in 26% and p53 positivity in 61% of all cases in a cohort of 43 patients with fallopian tube carcinoma. There was not significant correlation with survival (Lacy et al., 1995). Ovarian cancer in comparison also shows c-erbB-2 (HER-2/neu) positivity in about 29% of all cases (Lanitis et al., 2012). Others, in contrast, described a correlation between p53 immunohistochemical positivity and shorter survival (Zheng et al., 1997; Rosen et al., 2000). FIGO stages, however, did not correlate with survival in this same cohort of 63 patients (Rosen et al., 2000). Zheng et al. investigated the correlating immunohistochemistry and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) for p53 in 52 cases of fallopian tube carcinoma and 10 normal fallopian tubes and found that p53 alterations already occur at early stages suggesting a role in early tumor progression (Zheng et al., 1997). Chung and colleagues found that survival neither correlated with immunohistochemical p53 positivity nor with cMyc overexpression (which occured in 61%). However, the statistical power of this study was limited by the small cohort of 18 patients (Chung et al., 2000). Hence, it did not challenge larger studies which proposed that p53 might have an important role especially in familial BRCA-associated cases of fallopian tube carcinomas. Figure 2 shows different pathohistological aspects of a serous adenocarcinoma of the fallopian tube. Mixed epithelial-mesenchymal tumors The least common site for malignant Müllerian mixed tumor (carcinosarcoma, metaplastic carcinoma) is the fallopian tube accounting for only 4% of all cases. The prognosis of these mostly postmenopausal patients is poor (Hanjani et al., 1980). In the literature, only one adenosarcoma has been described in the fallopian tube (Gollard et al., 1995). Soft tissue tumors Leiomyosarcomas are very rare as only 37 cases have been reported in 100 years (Jacoby et al., 1993). Mesothelial tumors Adenomatoid tumors mostly occur in middle-aged or elderly women (Inoue et al., 2001). In most cases, they remain asymptomatic but can also occlude the lumen. Often, they show gland-like structures with a lining of flat to cuboidal cells (Stephenson and Mills, 1986). Germ cell tumors Until 2003, 50 cases of mature or immature teratoma were reported (Alvarado-Cabrero et al., 2003). For malignant mixed germ cell tumors of the fallopian tube, only one single case was published (Li et al., 1999). Trophoblastic tumors Only about 4% of choriocarcinomas occur in the fallopian tube (Dekel et al., 1986). About 40% of these go along with adnexal tumors (Ober and Maier, 1981). In the fallopian tube, hydatiform moles can histologically correspond to a complete, partial or invasive mole (Alvarado-Cabrero et al., 2003). Placental site nodules as non-neoplastic proliferation of intermediate trophoblast can occur (Alvarado-Cabrero et al., 2003). Intermediate trophoblast tumors can be either benign or malignant (Kurman et al., 1976). Only one case of malignant placental site trophoblastic tumor has been reported in the fallopian tube (Su et al., 1999). Lymphoid and haematopoietic tumors Malignant lymphoma and leukemia mostly show an involvement of the ipsilateral ovary (Osborne and Robboy, 1983). 25% of patients with ovary lymphomas had a Burkitt-lymphoma or Burkitt-like lymphoma or a diffuse large-cell lymphoma. Metastatic tumors For 89% of secondary tumors in the fallopian tube, the primary tumor was assigned to be of ovarian origin (Woodruff and Julian, 1969). Considering the ongoing paradigm shift which proposes that serous ovarian carcinomas likely originate from the fallopian tube, these figures have to be reconsidered. Many of these tumors may have originated from the fimbriated end of the fallopian tube with a secondary manifestation in the ovary.
	Table 3: Postoperative treatment of fallopian tube carcinoma (Pectasides et al., 2006).
Treatment	Surgical therapy: For fallopian tube tumors and especially for carcinomas, surgical removal is the first line treatment. Whereas benign tumors can usually be resected completely, the approach for fallopian tube carcinomas should be the same as for epithelial ovarian cancer with the aim of complete resection or at least maximum tumor debulking. Special focus should be placed on para-aortic and pelvic lymphadenectomy in regard to the higher rate of lymph node metastases (Yoonessi, 1979; McMurray et al., 1986; Maxson et al., 1987; Asmussen et al., 1988; Peters et al., 1988; Gadducci et al., 2001). Klein and colleagues found a significantly reduced median survival of 21 months versus 43 months in patients who had not undergone lymphadenectomy (Klein et al., 1999). Radiotherapy: Although radiotherapy for fallopian tube carcinomas could be considered, it is inferior to adjuvant platin compounds containing chemotherapy. Neither irradiation nor intraperitoneal instillation of radioisotopes could prevent relapse (Asmussen et al., 1988). A second look operation with pathological complete remission (pCR) is a predictor for longer survival. 50% of patients with surgical complete remission will ultimately relapse. Thus, second-look operations are not generally beneficial and hence no routine treatment (Takeshima and Hasumi, 2000). Adjuvant chemotherapy: Baekeland et al. found a 70% response rate to adjuvant platinum-containing chemotherapy in platinum-naive patients with median response duration of 12.5 months. They further suggested to refrain from postoperative radiation therapy due to its low efficacy and high rate of complications (Baekelandt et al., 2000). Kosary et al. gave the general recommendation to treat women with fallopian tube carcinomas like women with epithelial ovarian cancer, i.e. by surgical staging and debulking followed by adjuvant chemotherapy (Kosary and Trimble, 2002). In addition to platinum-based chemotherapy, also paclitaxel is becoming more and more important in the treatment of advanced fallopian tube tumors (Takeshima and Hasumi, 2000). Patients with early stages as IA and IB might not need adjuvant chemotherapy. For all higher stages, adjuvant combined chemotherapy is requested. Two randomized controlled trials (International Collaborative Ovarian Neoplasm 1 (ICON1) and Adjuvant Chemotherapy In Ovarian Neoplasm (ACTION)) compared platinum based adjuvant chemotherapy and mere observation after early stage ovarian cancer surgery and reported 5 year overall survival rates of 74% without and 82% with adjuvant platinum based chemotherapy (Trimbos et al., 2003). This could hint at a survival benefit being associated with adjuvant chemotherapy also for early stage fallopian tube carcinomas. Cisplatin based chemotherapy yielded response rates between 53 and 92 % (Deppe et al., 1980; Raju et al., 1981; McMurray et al., 1986; Maxson et al., 1987; Peters et al., 1988; King et al., 1989; Muntz et al., 1989; Barakat et al., 1993; Pectasides et al., 1994). Several studies also included Paclitaxel in the first line therapy (McMurray et al., 1986; Maxson et al., 1987; Muntz et al., 1991; Ben-Hur et al., 1999; Gemignani et al., 2001). For relapse therapy, data from epithelial ovarian cancer in platinum-pretreated patients also highlights the role of Paclitaxel (Tresukosol et al., 1995; Baekelandt et al., 2000; Ichikawa et al., 2000; Gemignani et al., 2001). After review of the literature and according to the U.S. guidelines, Pectasides and colleagues suggested an adjuvant standard treatment shown in table 3 (Pectasides et al., 2006). For the treatment of relapse, platinum-sensitive tumors (relapse after more than 6 months) receive a reinduction with platinum with or without Paclitaxel, whereas patients with platinum-refractory (relapse during therapy) or platinum-resistant tumors (relapse <6 months) receive Topotecan or liposomal Doxorubicin (Pectasides et al., 2006). In epithelial ovarian cancer, Bookman and colleagues as well as Hoskins et al. treated patients with relapse after platinum- and Paclitaxel-based chemotherapy with Topotecan (Bookman et al., 1998; Hoskins et al., 1998). Also liposomal Doxorubicin can achieve response rates of 17-26% in patients who have relapsed after platinum- and Paclitaxel based chemotherapy (Muggia et al., 1997; Gordon et al., 2000). Recent data from the OCEANS trial revealed that addition of Bevacizumab to the combination of carboplatinum/gemcitabine increases the response rate and prolongs progression-free survival in patients with platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian tube cancer. Overall survival, however, remained unchanged (Aghajanian et al., 2012). Likewise, the CALYPSO trial which tested the combination of pegylated liposomal doxorubicin (PLD)/carboplatin with paclitaxel/carboplatin in platinum-sensitive ovarian cancer patients found a prolonged time to progression along with reduced side effects of PLD as compared to paclitaxel. Again, however, there was no effect on overall survival (Wagner et al., 2012). Still, an intermediate report from the AURELIA trial suggests that supplementation of chemotherapy with Bevacizumab might be highly beneficial for patients with platinum-resistant ovarian cancer (Pujade-Lauraine et al., 2012).
Prognosis	Prognostic factors for early stage I carcinomas are depth of invasion into the tubal wall and tumor rupture during surgery. Even early stages tend to metastasize to the peritoneum (Baekelandt et al., 2000). The surgical stage is an independent prognostic factor (Alvarado-Cabrero et al., 1999; Baekelandt et al., 2000). Carcinomas of the fimbriae region are afflicted by a worse prognosis than carcinomas of the isthmic region (Alvarado-Cabrero et al., 1997). There are different results concerning the histological grading: Vaughan et al. found a significant correlation between grading and survival (Vaughan et al., 1998), Gadducci et al. could also find this in univariate but not in multivariate analysis (Gadducci et al., 2001). Grading further correlates with lymphogenous metastases (Klein et al., 1999). Lymphocytic infiltration of the tumor correlates with favorable outcome (Rosen et al., 1993). The role of DNA-ploidy is thought to be negligible (Klein et al., 2002). Fallopian tube carcinoma patients show an overall survival of 30-50% which is slightly better than the reported 25-40% for epithelial ovarian cancer (Momtazee and Kempson, 1968; Baekelandt et al., 1993; Barakat et al., 1993; Woolas et al., 1994; Alvarado-Cabrero et al., 1999; Piura and Rabinovich, 2000). The general 5-year survival rate is about 65% (Sedlis, 1978; Deppe et al., 1980; Inal et al., 2004). Kosary and colleagues found in a cohort of 416 women with fallopian tube carcinoma 5 year-survival rates of 95% for stage I (n=102), 75% for stage II (n=29), 69% for stage III (n= 52) and 45% for stage IV (n=151) (Kosary and Trimble, 2002).

Genetics

Note

Fallopian tube carcinomas can manifest as a consequence of the hereditary breast-ovarian cancer syndrome. They are associated with BRCA1 and BRCA2 mutations. In a cohort of 44 cases of fallopian tube carcinoma, 11% of the patients were positive for BRCA1 mutation and 5% were positive for BRCA2 mutations. Of the patients who received their diagnosis before the age of 55 years, 28% (5/18) were BRCA positive. First degree relatives of fallopian tube cancer patients show an increased risk for early breast and ovarian cancer (Aziz et al., 2001). A BRCA1-carrier patient undergoing prophylactic salpingo-oophorectomy showed a fallopian tube cancer (Hartley et al., 2000). A positive family history of fallopian tube carcinoma was predictive for BRCA1 mutation in 26 Canadian breast-ovarian cancer families (Tonin et al., 1995). Friedman et al. reported fallopian tube carcinomas in 2 of 12 families with BRCA1 mutations (Friedman et al., 1995). Tonin et al. found BRCA1 mutations in four Ashkenazi Jewish breast-ovarian cancer families with fallopian tube carcinoma (Tonin et al., 1996). Zweemer and colleagues detected fallopian tube carcinomas in 2 of 23 families with known BRCA1 mutations (Zweemer et al., 2000). Thus, genetic evaluation should become part of the diagnostics for patients with fallopian tube carcinomas. In risk patients, prophylactic oophorectomy should be accompanied by salpingectomy (Aziz et al., 2001). And whether salpingectomy without oophorectomy is sufficient treatment will be analyzed in the clinical trials yet to come. Jongsma and colleagues reported frequent loss of heterozygosity (LOH) on chromosome 13 in BRCA1-associated cases of fallopian tube carcinomas indicating that these areas may contain putative tumor suppressor genes (Jongsma et al., 2002). Different authors (see above) found that immunohistochemical or PCR-based positivity for p53 alterations correlates with shorter survival (Hellstrom et al., 1994; Zheng et al., 1997; Rosen et al., 2000).

Cytogenetics

Note

In BRCA1-related cases of ovarian and fallopian tube carcinoma, loss of heterozygosity (LOH) studies revealed high LOH frequencies on chromosome 13q11, 13q14, 13q21, 13q22-23, 13q32 and 13q32-4 that were independent of type of BRCA1 mutation, stage and grade. The authors suggested the long arm of chromosome 13 to contain putative tumor suppressor genes (Jongsma et al., 2002).

Genes involved and Proteins

Gene Name	BRCA1 (breast cancer 1, early onset)
Location	17q21.31
Dna / Rna	6 different mRNA variants that undergo alternative splicing. Splicing influences intracellular function and location. According to ENTREZ Gene, BRCA1 starts at NC_000017.10 (41196312..41277500, complement), Spidey (mRNA to genomic sequence alignment tool, http://www.ncbi.nlm.nih.gov/spidey) finds 24 exons. The mRNA consists of ~81.2kb.
Protein	The encoded protein functions as intracellular tumor suppressor with E3-ubiquitin ligase- and phosphopeptide binding activity. As a transcription factor, it is a DNA damage sensor forming (together with other proteins) the BRCA1-associated genome surveillance complex (BASC). Germline mutations lead to the familiar breast and ovarian cancer syndrome with highly increased risk for cancer development. Working together with RNA polymerase II, the protein has an important role in transcription, DNA repair of double-stranded breaks, and recombination. There are five different protein isoforms. Isoform 1 is the biggest with 1863 amino acids and 220 kDa. The highest expression of BRCA1 is found in the ovaries, thymus and testes.

Gene Name	BRCA2 (breast cancer 2, early onset)
Location	13q13.1
Dna / Rna	According to Spidey, BRCA2 has 27 exons. The mRNA spans about 84.2 kb. In exon 11, the BRC repeats are encoded.
Protein	Also BRCA2 is involved in DNA stability, especially the double strand repair. The several BRC motifs in the protein bind the RAD51 recombinase and thus enable DNA repair. The protein consists of 3418 amino acids with a weight of 384 kDa.

Gene Name	STK11 (serine/threonine kinase 11)
Location	19p13.3
Note	Mutation of this tumor suppressor gene causes the autosomal dominant Peutz-Jeghers-Syndrome which is characterized by intestinal polyposis and pigmented naevi as well as increased tumor risk (Jeghers et al., 1949; Giardiello et al., 1987). The protein is regulated by androgens and estrogen in adipocytes (McInnes et al., 2012).
Dna / Rna	The gene consists of 10 exons which encompass 23 kb.
Protein	The protein regulates cell polarity and functions as a tumor suppressor. It consists of 433 amino acids with a weight of 48.6 kDa.

Gene Name	ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian))
Location	17q12
Note	Other names: HER-2/neu, c-erbB-2.
Dna / Rna	31 exons, 2 mRNA variants encoding 2 proteins: isoform a and b.
Protein	This protein is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. It forms heterodimers with other EGFRs that (unlike ErbB-2) have a ligand binding domain and can thus initiate intracellular signaling leading to activation of pathways such as mTOR or PI3K. Overexpression is known for several cancers such as breast and ovarian but also fallopian tube carcinomas. Based on a cohort of 43 patients with fallopian tube carcinoma, Lacy et al. reported immunohistochemical positivity for c-erbB-2 (HER-2/neu) overexpression in 26% and p53 positivity in 61% of all cases. They could not find any correlation with survival (Lacy et al., 1995).

Gene Name	TP53 (Tumour protein p53 (Li-Fraumeni syndrome))
Location	17p13.1
Note	Tumor protein p53.
Dna / Rna	11 exons, 8 transcript variants encoding 7 protein isoforms (http://www.ncbi.nlm.nih.gov/gene/7157#reference-sequences).
Protein	p53 is a tumor suppressor protein that is synthesized in response to cellular stress. It causes cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism via DNA binding. The binding of p53 leads to transcriptional activation of several genes. Mutations are known from several human tumors and also for hereditary tumor syndroms like Li-Fraumeni-Syndrome. Transcription activation is triggered by a homo-tetrameric p53 complex in which mutant isoforms are dominant over the wild-type protein. Moreover, functional p53 induces its own degradation (with a half-life of 15-30 min) whereas mutant p53 accumulates and thus enables immunohistochemical detection. Examining a cohort of 43 patients with fallopian tube carcinoma, Lacy et al. found immunohistochemical positivity for c-erbB-2 (HER-2/neu) overexpression in 26% and p53 positivity in 61% of these tumors, but no significant correlation with survival (Lacy et al., 1995). Others, however, described p53 immunohistochemical positivity to be associated with shorter survival (Zheng et al., 1997; Rosen et al., 2000) whereas FIGO stages were not predictive for the outcome in this cohort of 63 patients (Rosen et al., 2000). Using 52 cases of fallopian tube carcinoma and 10 normal fallopian tubes, Zheng et al. investigated the p53 status based on immunohistochemistry and polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and suggested that p53 alterations play a role in early tumor progression as they are not restricted to late stages (Zheng et al., 1997). Chung and colleagues found that survival neither correlated with immunohistochemical p53 positivity nor with cMyc overexpression (which occured in 61%). However, the statistical power of this study was limited by the small cohort of 18 patients (Chung et al., 2000).

Gene Name	MYC v-myc myelocytomatosis viral oncogene homolog (avian)
Location	8q24.21
Dna / Rna	3 exons, 1 variant, 1 isoform.
Protein	The protein plays a role in cell cycle and apoptosis. It functions as transcription factor. Overexpression is known in several cancers especially leukaemias and lymphomas like Burkitt's lymphoma. Chung and colleagues found that survival neither correlated with immunohistochemical p53 positivity nor with cMyc overexpression (which occured in 61%). However, the statistical power of this study was limited by the small cohort of 18 patients (Chung et al., 2000).

To be noted

Acknowledgement: We would like to thank Prof. Dr. med. Eva Geißinger and Dr. med. Camelia-Maria Monoranu, Institute of Pathology at Würzburg University, for supporting this publication with histopathological material and helpful discussions.

Bibliography

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.

Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR.

J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23.

PMID 22529265

Primary fallopian tube carcinoma.

Ajithkumar TV, Minimole AL, John MM, Ashokkumar OS.

Obstet Gynecol Surv. 2005 Apr;60(4):247-52. (REVIEW)

PMID 15795632

Tumours of the Fallopian Tube.

Alvarado-Cabrero I, Cheung A, Caduff R.

World Health Organization classification of tumors: Tumors of the breast and female genital organs, IARC Press, 2003.

Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation.

Ambros RA, Sherman ME, Zahn CM, Bitterman P, Kurman RJ.

Hum Pathol. 1995 Nov;26(11):1260-7.

PMID 7590702

Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.

Amos CI, Bali D, Thiel TJ, Anderson JP, Gourley I, Frazier ML, Lynch PM, Luchtefeld MA, Young A, McGarrity TJ, Seldin MF.

Cancer Res. 1997 Sep 1;57(17):3653-6.

PMID 9288765

alpha-Fetoprotein-producing (hepatoid) carcinoma of the fallopian tube.

Aoyama T, Mizuno T, Andoh K, Takagi T, Mizuno T, Eimoto T.

Gynecol Oncol. 1996 Nov;63(2):261-6.

PMID 8910638

Primary adenocarcinoma localized to the fallopian tubes: report on 33 cases.

Asmussen M, Kaern J, Kjoerstad K, Wright PB, Abeler V.

Gynecol Oncol. 1988 Jun;30(2):183-6.

PMID 3371742

A genetic epidemiological study of carcinoma of the fallopian tube.

Aziz S, Kuperstein G, Rosen B, Cole D, Nedelcu R, McLaughlin J, Narod SA.

Gynecol Oncol. 2001 Mar;80(3):341-5.

PMID 11263928

Carcinoma of the fallopian tube.

Baekelandt M, Jorunn Nesbakken A, Kristensen GB, Trope CG, Abeler VM.

Cancer. 2000 Nov 15;89(10):2076-84.

PMID 11066048

Second-look laparotomy in carcinoma of the fallopian tube.

Barakat RR, Rubin SC, Saigo PE, Lewis JL Jr, Jones WB, Curtin JP.

Obstet Gynecol. 1993 Nov;82(5):748-51. (REVIEW)

PMID 8414320

Metaplastic papillary tumor of the fallopian tube. Case report, immunohistochemical features, and review of the literature.

Bartnik J, Powell WS, Moriber-Katz S, Amenta PS.

Arch Pathol Lab Med. 1989 May;113(5):545-7. (REVIEW)

PMID 2469407

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.

Bookman MA, Malmstrom H, Bolis G, Gordon A, Lissoni A, Krebs JB, Fields SZ.

J Clin Oncol. 1998 Oct;16(10):3345-52.

PMID 9779711

Clinical aspects of primary carcinoma of the Fallopian tube: a clinical study of 14 cases.

Boutselis JG, Thompson JN.

Am J Obstet Gynecol. 1971 Sep;111(1):98-101.

PMID 5096363

Ectopic pregnancy coexisting with a primary carcinoma of the Fallopian tube: a case report.

Carapeto R, Nogales FF Jr, Matilla A.

Int J Gynaecol Obstet. 1978-1979;16(3):263-4.

PMID 33091

Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention.

Carlson JW, Miron A, Jarboe EA, Parast MM, Hirsch MS, Lee Y, Muto MG, Kindelberger D, Crum CP.

J Clin Oncol. 2008 Sep 1;26(25):4160-5. doi: 10.1200/JCO.2008.16.4814.

PMID 18757330

Pseudocarcinomatous hyperplasia of the fallopian tube associated with salpingitis. A report of 14 cases.

Cheung AN, Young RH, Scully RE.

Am J Surg Pathol. 1994 Nov;18(11):1125-30.

PMID 7943533

Overexpression of p53 and HER-2/neu and c-myc in primary fallopian tube carcinoma.

Chung TK, Cheung TH, To KF, Wong YF.

Gynecol Obstet Invest. 2000;49(1):47-51.

PMID 10629373

Challenges in the early diagnosis and staging of Fallopian-tube carcinomas associated with BRCA mutations.

Colgan TJ.

Int J Gynecol Pathol. 2003 Apr;22(2):109-20. (REVIEW)

PMID 12649664

Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: a report of six cases.

Daya D, Young RH, Scully RE.

Int J Gynecol Pathol. 1992;11(2):122-30.

PMID 1582746

Primary choriocarcinoma of the fallopian tube. Report of a case with survival and postoperative delivery. Review of the literature.

Dekel A, van Iddekinge B, Isaacson C, Dicker D, Feldberg D, Goldman J.

Obstet Gynecol Surv. 1986 Mar;41(3):142-8.

PMID 3960415

Clues to the pathogenesis of fallopian tube carcinoma: a morphological and immunohistochemical case control study.

Demopoulos RI, Aronov R, Mesia A.

Int J Gynecol Pathol. 2001 Apr;20(2):128-32.

PMID 11293157

Combination chemotherapy for advanced carcinoma of the fallopian tube.

Deppe G, Bruckner HW, Cohen CJ.

Obstet Gynecol. 1980 Oct;56(4):530-2.

PMID 7191548

The post-reproductive Fallopian tube: better removed?

Dietl J, Wischhusen J, Hausler SF.

Hum Reprod. 2011 Nov;26(11):2918-24. doi: 10.1093/humrep/der274. Epub 2011 Aug 16. (REVIEW)

PMID 21849300

Primary adenomyoma of the fallopian tube mimicking tubal malignant tumor.

Etoh T, Watanabe Y, Imaoka I, Murakami T, Hoshiai H.

J Obstet Gynaecol Res. 2012 Apr;38(4):721-3. doi: 10.1111/j.1447-0756.2011.01764.x. Epub 2012 Mar 2.

PMID 22380532

Precursors to pelvic serous carcinoma and their clinical implications.

Folkins AK, Jarboe EA, Roh MH, Crum CP.

Gynecol Oncol. 2009 Jun;113(3):391-6. doi: 10.1016/j.ygyno.2009.01.013. Epub 2009 Feb 23. (REVIEW)

PMID 19237187

Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

Friedman LS, Szabo CI, Ostermeyer EA, Dowd P, Butler L, Park T, Lee MK, Goode EL, Rowell SE, King MC.

Am J Hum Genet. 1995 Dec;57(6):1284-97.

PMID 8533757

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

Gadducci A, Landoni F, Sartori E, Maggino T, Zola P, Gabriele A, Rossi R, Cosio S, Fanucchi A, Tisi G.

Gynecol Oncol. 2001 May;81(2):150-9.

PMID 11330942

Paclitaxel-based chemotherapy in carcinoma of the fallopian tube.

Gemignani ML, Hensley ML, Cohen R, Venkatraman E, Saigo PE, Barakat RR.

Gynecol Oncol. 2001 Jan;80(1):16-20.

PMID 11136563

Increased risk of cancer in the Peutz-Jeghers syndrome.

Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD.

N Engl J Med. 1987 Jun 11;316(24):1511-4.

PMID 3587280

Obstructing fallopian tube papilloma.

Gisser SD.

Int J Gynecol Pathol. 1986;5(2):179-82.

PMID 3721698

Two unusual presentations of mullerian adenosarcoma: case reports, literature review, and treatment considerations.

Gollard R, Kosty M, Bordin G, Wax A, Lacey C.

Gynecol Oncol. 1995 Dec;59(3):412-22. (REVIEW)

PMID 8522267

Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer.

Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Rosales R, Sharpington T.

J Clin Oncol. 2000 Sep;18(17):3093-100.

PMID 10963637

Immunohistochemical profile of serous papillary cystadenofibroma of the fallopian tube: a clue of paramesonephritic origin.

Gurbuz Y, Ozkara SK.

Appl Immunohistochem Mol Morphol. 2003 Jun;11(2):153-5.

PMID 12778000

Malignant mixed Mullerian tumor of the fallopian tube. Report of a case and review of literature.

Hanjani P, Petersen RO, Bonnell SA.

Gynecol Oncol. 1980 Jun;9(3):381-93.

PMID 6247252

Clear cell carcinoma of the fimbria of the fallopian tube in a BRCA1 carrier undergoing prophylactic surgery.

Hartley A, Rollason T, Spooner D.

Clin Oncol (R Coll Radiol). 2000;12(1):58-9.

PMID 10749023

Polyp of the fallopian tube.

Heatley MK.

Pathology. 2001 Nov;33(4):538-9.

PMID 11827429

Adenomatous polyp of the fallopian tube. A case report.

Heller DS, Rubinstein N, Dikman S, Deligdisch L, Moss R.

J Reprod Med. 1991 Jan;36(1):82-4.

PMID 2008008

DNA-ploidy and mutant p53 overexpression in primary fallopian tube cancer.

Hellstrom AC, Hue J, Silfversward C, Auer G.

Int J Gynecol Cancer. 1994 Nov;4(6):408-413.

PMID 11578443

Primary carcinoma of the fallopian tube: difficulties of diagnosis and treatment.

Henderson SR, Harper RC, Salazar OM, Rudolph JH.

Gynecol Oncol. 1977 Jun;5(2):168-79.

PMID 195869

Clinical study of primary carcinoma of the fallopian tube: experience with 15 cases.

Hirai Y, Kaku S, Teshima H, Shimizu Y, Chen JT, Hamada T, Fujimoto I, Yamauchi K, Sakamoto A, Hasumi K, et al.

Gynecol Oncol. 1989 Jul;34(1):20-6.

PMID 2737521

Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.

Hoskins P, Eisenhauer E, Beare S, Roy M, Drouin P, Stuart G, Bryson P, Grimshaw R, Capstick V, Zee B.

J Clin Oncol. 1998 Jun;16(6):2233-7.

PMID 9626225

Metachronous carcinoma of the vulva and fallopian tube.

Ichikawa Y, Tsunoda H, Nishide K, Nishida M, Kubo T.

Gynecol Oncol. 2000 Apr;77(1):206-9.

PMID 10739714

Fallopian tube malignancies: experience of Social Security Agency Aegean Maternity Hospital.

Inal MM, Hanhan M, PIlanci B, Tinar S.

Int J Gynecol Cancer. 2004 Jul-Aug;14(4):595-9.

PMID 15304152

Tubal ectopic pregnancy associated with an adenomatoid tumor.

Inoue T, Nabeshima K, Shimao Y, Akiyama Y, Ohtsuka T, Koono M.

Pathol Int. 2001 Mar;51(3):211-4.

PMID 11328538

Primary leiomyosarcoma of the fallopian tube.

Jacoby AF, Fuller AF Jr, Thor AD, Muntz HG.

Gynecol Oncol. 1993 Dec;51(3):404-7. (REVIEW)

PMID 8112653

Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance.

Jeghers H, McKusick VA, Katz KH.

N Engl J Med. 1949 Dec 29;241(26):1031-6.

PMID 15398245

Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer.

Jongsma AP, Piek JM, Zweemer RP, Verheijen RH, Klein Gebbinck JW, van Kamp GJ, Jacobs IJ, Shaw P, van Diest PJ, Kenemans P.

Mol Pathol. 2002 Oct;55(5):305-9.

PMID 12354934

Metaplastic papillary tumor of the fallopian tube: a case report with ultrastructure.

Keeney GL, Thrasher TV.

Int J Gynecol Pathol. 1988;7(1):86-92.

PMID 3350619

High-grade serous ovarian cancer arises from fallopian tube in a mouse model.

Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM.

Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3921-6. doi: 10.1073/pnas.1117135109. Epub 2012 Feb 13.

PMID 22331912

Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship.

Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP.

Am J Surg Pathol. 2007 Feb;31(2):161-9.

PMID 17255760

Fallopian tube carcinoma: a clinicopathological study of 17 cases.

King A, Seraj IM, Thrasher T, Slater J, Wagner RJ.

Gynecol Oncol. 1989 Jun;33(3):351-5.

PMID 2722062

Tumor progression, histologic grading and DNA-ploidy as predictive factors of lymphogenous metastasis in primary carcinoma of the Fallopian tube.

Klein M, Graf AH, Rosen A, Lahousen M, Hacker GW.

Cancer Lett. 2002 Mar 28;177(2):209-14.

PMID 11825669

Lymphadenectomy in primary carcinoma of the Fallopian tube.

Klein M, Rosen AC, Lahousen M, Graf AH, Rainer A.

Cancer Lett. 1999 Dec 1;147(1-2):63-6.

PMID 10660090

Treatment and survival for women with Fallopian tube carcinoma: a population-based study.

Kosary C, Trimble EL.

Gynecol Oncol. 2002 Aug;86(2):190-1.

PMID 12144827

Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.

Kuhn E, Meeker A, Wang TL, Sehdev AS, Kurman RJ, Shih IeM.

Am J Surg Pathol. 2010 Jun;34(6):829-36. doi: 10.1097/PAS.0b013e3181dcede7.

PMID 20431479

Trophoblastic pseudotumor of the uterus: an exaggerated form of "syncytial endometritis" simulating a malignant tumor.

Kurman RJ, Scully RE, Norris HJ.

Cancer. 1976 Sep;38(3):1214-26.

PMID 182351

c-erbB-2 and p53 expression in fallopian tube carcinoma.

Lacy MQ, Hartmann LC, Keeney GL, Cha SC, Wieand HS, Podratz KC, Roche PC.

Cancer. 1995 Jun 15;75(12):2891-6.

PMID 7773939

Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels.

Lanitis E, Dangaj D, Hagemann IS, Song DG, Best A, Sandaltzopoulos R, Coukos G, Powell DJ Jr.

PLoS One. 2012;7(11):e49829. doi: 10.1371/journal.pone.0049829. Epub 2012 Nov 26.

PMID 23189165

A candidate precursor to serous carcinoma that originates in the distal fallopian tube.

Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, Garber J, Birch C, Mou H, Gordon RW, Cramer DW, McKeon FD, Crum CP.

J Pathol. 2007 Jan;211(1):26-35.

PMID 17117391

Paraneoplastic cerebellar degeneration heralding fallopian tube adenocarcinoma.

Levite R, Fishman A, Kesler A, Altaras M, Gadoth N.

Int J Gynecol Cancer. 2001 Mar-Apr;11(2):169-71.

PMID 11328418

Mixed malignant germ cell tumor of the fallopian tube.

Li S, Zimmerman RL, LiVolsi VA.

Int J Gynecol Pathol. 1999 Apr;18(2):183-5.

PMID 10202679

Primary carcinoma of the fallopian tube: evidence for activity of cisplatin combination therapy.

Maxson WZ, Stehman FB, Ulbright TM, Sutton GP, Ehrlich CE.

Gynecol Oncol. 1987 Mar;26(3):305-13.

PMID 3557196

A fallopian tube lesion of borderline malignancy associated with pseudo-myxoma peritonei.

McCarthy JH, Aga R.

Histopathology. 1988 Aug;13(2):223-5.

PMID 3169690

Regulation of LKB1 expression by sex hormones in adipocytes.

McInnes KJ, Brown KA, Hunger NI, Simpson ER.

Int J Obes (Lond). 2012 Jul;36(7):982-5. doi: 10.1038/ijo.2011.172. Epub 2011 Aug 30.

PMID 21876548

Carcinoma of the fallopian tube. Management and sites of failure.

McMurray EH, Jacobs AJ, Perez CA, Camel HM, Kao MS, Galakatos A.

Cancer. 1986 Nov 1;58(9):2070-5.

PMID 3756822

Primary adenocarcinoma of the fallopian tube.

Momtazee S, Kempson RL.

Obstet Gynecol. 1968 Nov;32(5):649-56.

PMID 5742479

Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.

Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang LJ.

J Clin Oncol. 1997 Mar;15(3):987-93.

PMID 9060537

Combination chemotherapy in advanced adenocarcinoma of the fallopian tube.

Muntz HG, Tarraza HM, Goff BA, Granai GO, Rice LW, Nikrui N, Fuller AF Jr.

Gynecol Oncol. 1991 Mar;40(3):268-73.

PMID 2013452

Endometrioid carcinoma of the fallopian tube: a clinicopathologic analysis of 26 cases.

Navani SS, Alvarado-Cabrero I, Young RH, Scully RE.

Gynecol Oncol. 1996 Dec;63(3):371-8.

PMID 8946874

Cancer staging manual.

No authors listed.

Springer NY Dordrecht Heidelberg London. AJCC (2010).

Gestational choriocarcinoma of the fallopian tube.

Ober WB, Maier RC.

Diagn Gynecol Obstet. 1981 Fall;3(3):213-31. (REVIEW)

PMID 7035113

Lymphomas or leukemia presenting as ovarian tumors. An analysis of 42 cases.

Osborne BM, Robboy SJ.

Cancer. 1983 Nov 15;52(10):1933-43.

PMID 6627208

Fallopian tube carcinoma: a review.

Pectasides D, Pectasides E, Economopoulos T.

Oncologist. 2006 Sep;11(8):902-12. (REVIEW)

PMID 16951394

Prognostic features of carcinoma of the fallopian tube.

Peters WA 3rd, Andersen WA, Hopkins MP, Kumar NB, Morley GW.

Obstet Gynecol. 1988 May;71(5):757-62.

PMID 3357664

Ovarian carcinogenesis: an alternative hypothesis.

Piek JM, van Diest PJ, Verheijen RH.

Adv Exp Med Biol. 2008;622:79-87. doi: 10.1007/978-0-387-68969-2_7. (REVIEW)

PMID 18546620

Primary carcinoma of the fallopian tube: study of 11 cases.

Piura B, Rabinovich A.

Eur J Obstet Gynecol Reprod Biol. 2000 Aug;91(2):169-75.

PMID 10869791

Are all pelvic (nonuterine) serous carcinomas of tubal origin?

Przybycin CG, Kurman RJ, Ronnett BM, Shih IeM, Vang R.

Am J Surg Pathol. 2010 Oct;34(10):1407-16. doi: 10.1097/PAS.0b013e3181ef7b16.

PMID 20861711

AURELIA: A randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC).

Pujade-Lauraine E, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote IB, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag DT, Ray-Coquard I, AURELIA Investigators.

ASCO 2012 Annual Meeting.

Immunohistochemical staining for CA-125 in fallopian tube carcinomas.

Puls LE, Davey DD, DePriest PD, Gallion HH, van Nagell JR Jr, Hunter JE, Pavlik EJ.

Gynecol Oncol. 1993 Mar;48(3):360-3.

PMID 8462903

Primary carcinoma of the fallopian tube. Report of 22 cases.

Raju KS, Barker GH, Wiltshaw E.

Br J Obstet Gynaecol. 1981 Nov;88(11):1124-9.

PMID 7295603

Sociodemographic determinants of incidence of primary fallopian tube carcinoma, Finland 1953-97.

Riska A, Leminen A, Pukkala E.

Int J Cancer. 2003 May 1;104(5):643-5.

PMID 12594821

Fallopian tube cancer. The Roswell Park experience.

Rose PG, Piver MS, Tsukada Y.

Cancer. 1990 Dec 15;66(12):2661-7.

PMID 2249208

Primary carcinoma of the fallopian tube--a retrospective analysis of 115 patients. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

Rosen A, Klein M, Lahousen M, Graf AH, Rainer A, Vavra N.

Br J Cancer. 1993 Sep;68(3):605-9.

PMID 8353051

p53 expression in fallopian tube carcinomas.

Rosen AC, Ausch C, Klein M, Graf AH, Metzenbauer M, Philipp K, Reiner A.

Cancer Lett. 2000 Aug 1;156(1):1-7.

PMID 10840153

Management and prognosis of primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

Rosen AC, Klein M, Hafner E, Lahousen M, Graf AH, Reiner A.

Gynecol Obstet Invest. 1999;47(1):45-51.

PMID 10026026

Incidence of malignant fallopian tube tumors.

Rosenblatt KA, Weiss NS, Schwartz SM.

Gynecol Oncol. 1989 Nov;35(2):236-9.

PMID 2807017

Metaplastic papillary tumor of the fallopian tube--a distinctive lesion of pregnancy.

Saffos RO, Rhatigan RM, Scully RE.

Am J Clin Pathol. 1980 Aug;74(2):232-6.

PMID 7405904

Staging and prognosis in primary carcinoma of the fallopian tube.

Schiller HM, Silverberg SG.

Cancer. 1971 Aug;28(2):389-95.

PMID 5566359

Primary carcinoma of the fallopian tube. A report of 19 cases with literature review.

Schneider C, Wight E, Perucchini D, Haller U, Fink D.

Eur J Gynaecol Oncol. 2000;21(6):578-82. (REVIEW)

PMID 11214613

Carcinoma of the fallopian tube.

Sedlis A.

Surg Clin North Am. 1978 Feb;58(1):121-9.

PMID 644422

"Primary peritoneal" high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer.

Seidman JD, Zhao P, Yemelyanova A.

Gynecol Oncol. 2011 Mar;120(3):470-3. doi: 10.1016/j.ygyno.2010.11.020. Epub 2010 Dec 14.

PMID 21159368

Mucinous lesions of the fallopian tube. A report of seven cases.

Seidman JD.

Am J Surg Pathol. 1994 Dec;18(12):1205-12.

PMID 7977943

Anti-Yo antibody associated with occult fallopian tube carcinoma.

Selby KJ, Warner J, Klempner S, Konstantinopoulos PA, Hecht JL.

Int J Gynecol Pathol. 2011 Nov;30(6):536-8. doi: 10.1097/PGP.0b013e3182237ca6.

PMID 21979588

Adenomatoid tumours: an immunohistochemical and ultrastructural appraisal of their histogenesis.

Stephenson TJ, Mills PM.

J Pathol. 1986 Apr;148(4):327-35.

PMID 3517266

The incidence of primary fallopian tube cancer in the United States.

Stewart SL, Wike JM, Foster SL, Michaud F.

Gynecol Oncol. 2007 Dec;107(3):392-7. Epub 2007 Oct 24.

PMID 17961642

Pregnancy with primary tubal placental site trophoblastic tumor--A case report and literature review.

Su YN, Cheng WF, Chen CA, Lin TY, Hsieh FJ, Cheng SP, Hsieh CY.

Gynecol Oncol. 1999 May;73(2):322-5. (REVIEW)

PMID 10329055

Treatment of fallopian tube cancer. Review of the literature.

Takeshima N, Hasumi K.

Arch Gynecol Obstet. 2000 Jul;264(1):13-9. (REVIEW)

PMID 10985612

Adenocarcinoma of the uterine tube: potential for lymph node metastases.

Tamimi HK, Figge DC.

Am J Obstet Gynecol. 1981 Sep 15;141(2):132-7.

PMID 7282787

Paraneoplastic cerebellar degeneration with fallopian tube adenocarcinoma.

Tanaka Y, Suzuki N, Takao M, Ichikawa A, Susumu N, Aoki D.

Gynecol Oncol. 2005 Nov;99(2):500-3. Epub 2005 Aug 29.

PMID 16126258

Linkage analysis of 26 Canadian breast and breast-ovarian cancer families.

Tonin P, Moslehi R, Green R, Rosen B, Cole D, Boyd N, Cutler C, Margolese R, Carter R, McGillivray B, et al.

Hum Genet. 1995 May;95(5):545-50.

PMID 7759076

Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families.

Tonin P, Weber B, Offit K, Couch F, Rebbeck TR, Neuhausen S, Godwin AK, Daly M, Wagner-Costalos J, Berman D, Grana G, Fox E, Kane MF, Kolodner RD, Krainer M, Haber DA, Struewing JP, Warner E, Rosen B, Lerman C, Peshkin B, Norton L, Serova O, Foulkes WD, Garber JE, et al.

Nat Med. 1996 Nov;2(11):1179-83. (REVIEW)

PMID 8898735

Primary fallopian tube adenocarcinoma: clinical complete response after salvage treatment with high-dose paclitaxel.

Tresukosol D, Kudelka AP, Edwards CL, Fromm GL, Mante R, Kavanagh JJ.

Gynecol Oncol. 1995 Aug;58(2):258-61.

PMID 7622116

International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma.

Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; European Organisation for Research and Treatment of Cancer Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm.

J Natl Cancer Inst. 2003 Jan 15;95(2):105-12.

PMID 12529343

Transitional cell carcinoma pattern in primary carcinoma of the fallopian tube.

Uehira K, Hashimoto H, Tsuneyoshi M, Enjoji M.

Cancer. 1993 Oct 15;72(8):2447-56.

PMID 8402462

Fallopian tube precursors of ovarian low- and high-grade serous neoplasms.

Vang R, Shih IeM, Kurman RJ.

Histopathology. 2013 Jan;62(1):44-58. doi: 10.1111/his.12046.

PMID 23240669

Diseases of the fallopian tube and paratubal region.

Vang RWJ.

Blaustein's pathology of the female genital tract. New York, Springer. 2011.

Survival of patients with primary fallopian tube carcinoma.

Vaughan MM, Evans BD, Baranyai J, Weitzer MJ.

Int J Gynecol Cancer. 1998 Jan;8(1):16-22.

PMID 11576282

Primary clear cell adenocarcinoma of the fallopian tube: light microscopic and ultrastructural findings.

Voet RL, Lifshitz S.

Int J Gynecol Pathol. 1982;1(3):292-8.

PMID 7185764

Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients.

Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP.

Br J Cancer. 2012 Aug 7;107(4):588-91. doi: 10.1038/bjc.2012.307. Epub 2012 Jul 26.

PMID 22836511

Multiple malignancy in the upper genital canal.

Woodruff JD, Julian CG.

Am J Obstet Gynecol. 1969 Mar 15;103(6):810-22.

PMID 5765964

What is the true incidence of primary fallopian tube carcinoma?

Woolas R, Jacobs I, Davies AP, Leake J, Brown C, Grudzinskas JG, Oram D.

Int J Gynecol Cancer. 1994 Nov;4(6):384-388.

PMID 11578438

The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube.

Xian W, Miron A, Roh M, Semmel DR, Yassin Y, Garber J, Oliva E, Goodman A, Mehra K, Berkowitz RS, Crum CP, Quade BJ.

J Pathol. 2010 Jan;220(1):17-23. doi: 10.1002/path.2624.

PMID 19834951

Carcinoma of the fallopian tube.

Yoonessi M.

Obstet Gynecol Surv. 1979 Apr;34(4):257-70.

PMID 471364

An unusual case of a renin-producing tumour of the fallopian tube.

Zabernigg A, Muller-Holzner E, Gasc JM, Gattringer C.

Eur J Cancer. 1997 Sep;33(10):1709.

PMID 9389939

Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube.

Zheng W, Sung CJ, Cao P, Zhang ZF, Cai R, Godwin TA, Kramer EE, Lauchlan SC.

Gynecol Oncol. 1997 Jan;64(1):38-48.

PMID 8995545

Borderline papillary serous tumour of the fallopian tube.

Zheng W, Wolf S, Kramer EE, Cox KA, Hoda SA.

Am J Surg Pathol. 1996 Jan;20(1):30-5.

PMID 8540606

Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations.

Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, Jacobs IJ, Menko FH, Kenemans P.

Gynecol Oncol. 2000 Jan;76(1):45-50.

PMID 10620440

Citation

This paper should be referenced as such :

Stein, RG ; Diessner, J ; Hönig, A ; Wischhusen, J ; Dietl, J

Fallopian tube tumors: an overview

Atlas Genet Cytogenet Oncol Haematol. 2013;17(11):773-787.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/FallopTubTumID5279.html

External links

arrayMap	Topo ( C57) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease database	Fallopian tube tumors: an overview

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed

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