1.Tumour Molecular Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK
For ovarian sex cord-stromal tumours these include:
There have also been accounts of fibromas, a type of sex cord-stromal tumour affecting more than one family member, implying a genetic predisposition in a subset of cases.
about 5-10% of ovarian epithelial tumours are associated with one of three syndromes:
Epidemiology studies have shown a correlation between increased risk of ovarian epithelial tumours with increased number of ovulation cycles. Other factors which increase the likelihood of developing ovarian epithelial tumours include: use of talc on perineum and vulva, asbestos, pelvic irradiation, viruses, high-fat diet and lactose consumption. Reducing the number of ovulation cycles by multiparity, breast-feeding and oral contraceptives, decreases the probability of ovarian cancer.
There is no racial predisposition to ovarian sex cord-stromal tumours or ovarian germ cell tumours. However there is a racial predisposition for ovarian epithelial tumours with higher risks for Caucasians and lower risks for black women. Clear cell adenocarcinoma, a subtype of ovarian epithelial tumours, is more prevalent in Japanese than in Western women.
Ovarian germ cell tumours are highly responsive to chemotherapy and radiotherapy, although the former is preferable in order to conserve ovarian function. Ovarian epithelial tumours are initially highly responsive to chemotherapy, but most patients relapse and fail to respond to subsequent chemotherapy regimes. Postoperative radiotherapy is also provided for ovarian adenocarcinoma patients in order to treat minimal residual disease. Platinum-based chemotherapy is used to treat both ovarian germ cell and epithelial tumours. There is very little data available on the treatment of advanced/recurrent ovarian sex cord-stromal tumours due to their rarity and varied indolence, but some responses have been obtained with combination chemotherapy in each subtype. However there is currently no effective treatment for metastatic lipid cell tumours.
Meanwhile the situation is very different in ovarian carcinomas, which often present at advanced stages with extensive metastases. If ovarian epithelial tumours are diagnosed at stage I (growth limited to the ovaries), 5-year survival rates are >90%, in stark contrast to
There is far more cytogenetic data available on ovarian carcinomas (epithelial tumours) due to their higher incidences, with over 400 published karyotypes. Published cytogenetic data on ovarian epithelial tumours are detailed on Mitelman Database of Chromosome Aberrations in Cancer. The cytogenetic aberrations are non-random and complex. However, no pathognomonic rearrangements have been identified thus far. The karyotypes often show severe aneuploidy, with hypodiploid or near-triploid stemline chromosome numbers. The different subtypes of ovarian carcinoma show no marked cytogenetic differences, except seropapillary tumours more frequently display chromosome aberrations than the other subtypes. A correlation exists between karyotypic complexity and tumour grade. Simple chromosome changes (numerical changes only or a single structural rearrangement) were found in well-differentiated carcinomas, whereas complex karyotypes were found in poorly differentiated tumours. Patients with aberrant tumour karyotypes, particularly complex ones, were associated with short survival. The most prevalent numerical changes are gains of chromosomes 1, 2, 3, 6, 7, 9, 12 and 20 losses of chromosomes 4, 8, 11, 13, 14, 15, 17 and 22. Structural rearrangements primarily involve deletions and unbalanced translocations involving 1p, 1q, 3p, 3q, 6q, 7p, 10q, 11p, 11q and 12q.
In contrast, there is a plethora of CGH and allelotyping data implicating many genomic regions in ovarian epithelial tumours. Interphase cytogenetics demonstrated a high frequency of gain of copy number of 20q13.2 (70%), AIB1 (20q12) and cyclin D1 (CCND1 at 11q13, 72%) in ovarian epithelial tumours which were associated with poor prognosis. For a comprehensive overview of the imbalances identified by CGH in published reports of ovarian epithelial tumours see http://www.helsinki.fi/cmg/cgh_data.html. The commonest imbalances detected by CGH of epithelial neoplasms were gains of 8q, 1q, 20q, 3q and 19p in 69-53% of a series of 106 tumours and under-representations of 13q, 4q and 18q in 54-50% of cases. Under-representation of 11p and 13q and over-representation of 8q and 7q correlated with undifferentiated ovarian carcinoma, whereas 12p under-representation and 18p over-representation were more commonly associated with well-differentiated and moderately differentiated tumours. In a study correlating CGH genomic imbalances with clinical endpoints in 60 ovarian carcinomas, the following associations were found:
Lisa Lee-Jones
Ovarian tumours : an overview
Atlas Genet Cytogenet Oncol Haematol. 2003-12-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5231/gene-explorer/case-report-explorer/img/logo-atlas-4.svg