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Uterus: Carcinoma of the cervix

Written1999-09Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK
Updated2000-05Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C530-C531,C538-C539 CERVIX UTERI
Atlas_Id 5046
Phylum Female organs: Uterus::Uterine Cervix Neoplasia

Classification

Note
  • squamous cell carcinoma (80%)
  • adenocarcinoma (10%)
  • adenoacanthoma (10%)
  • Clinics and Pathology

    Disease carcinoma of the cervix uteri; usually arises in the transitional zone between squamous and columnar cell epithelium
    Etiology infection with high-risk forms of the human papillomavirus (HPV) is established as the major factor: a secondary factor is cigarette smoking; recent evidence suggests that a polymorphic variant of the tumour suppressor P53 (p53Arg) may represent a risk factor for cervical carcinogenesis
    Epidemiology over 470,000 new cases are diagnosed annually worldwide
    Clinics haematuria
    Cytology cervical smears confirm the diagnosis of carcinoma or may reveal the presence of the disease in its preinvasive (preclinical) stage
    Pathology three grades of preinvasive carcinoma-in-situ (CIN) are recognised: I (which usually undergoes spontaneous resolution), II and III;
    carcinomas are staged as follows:
  • IA: early invasive, not grossly visible;
  • IB: usually grossly visible, but confined to the cervix;
  • IIA: spread to the upper two thirds of the vagina only;
  • IIB: lateral extension into the parametrium;
  • IIIA: involvement of the lowest third of the vagina;
  • IIIB: involvement of the pelvic side wall or hydronephrosis;
  • IVA: bladder or rectal involvement;
  • IVB: distant metastasis
  • Treatment radiotherapy and/or surgery; late stages: radiotherapy supplemented by chemotherapy (e.g. cisplatin)
    Evolution preinvasive stage, detectable by cervical cytology, shows a peak incidence between 25 and 40 years; that of invasive cancer is 40-50 years, thus indicating that the preinvasive usually progresses to the invasive stage over a very prolonged period
    Prognosis preinvasive lesions are curable by local removal; stage I and early IIA cases may expect 80-90% five year survival; later cases show survival rates of 65-20% or less

    Cytogenetics

    Note polyploidisation, with modes in the triploid region or above, is common, particularly in the preinvasive phase where it may be linked to the frequent spindle anomalies that result, for instance, in the three group metaphases seen in histological sections and chromosome preparations; structural changes are commonest in chromosomes 1, 3, 5, 11 and 17 where, except in chromosome 5, they most often result in short-arm deletions
    Cytogenetics
    Morphological
  • Chromosome 1: changes may also result in the acquisition of additional long-arm material (as is common in other types of carcinoma), e.g. in the form of a 1q isochromosome
  • Chromosome 3: additional material on 3q has been shown by comparative genomic hybridization (CGH) in 90% of carcinomas and this gain may occur at the point of transition from severe dysplasia to invasive carcinoma; recent studies suggest involvement of the hTR gene which encodes the RNA component of telomerase; loss of heterozygosity (LOH) studies indicate that there are two regions on 3p where tumour suppressor genes may be situated: at 3pl4.2 (FHIT gene) and at 3q21, gene not yet identified
  • Chromosome 4: LOH studies suggest that at least two genes are important, at 4p16 and 4q21-35
  • Chromosome 5: an i(5p), often in two or more copies, is a frequent finding in cervical carcinomas, and this is consistent with CGH studies which show amplification of 5p, particularly in advanced stages
  • Chromosome 6: LOH studies show a high frequency of loss in the region 6p21.3-p25
  • Chromosome 11: possible gene loss on both chromosome arms are suggested by LOH studies, at 11p15 and 11q23; identities of the genes have yet to be determined
  • Chromosome 17: G-banding and LOH studies have shown the nonrandom loss of 17q, where the P53 gene is situated (at 17p13.3); mutations or loss of this gene are, however, relatively infrequent compared with other types of tumour, perhaps because there is instead interaction between p53 protein and the HPV E6 viral gene in most carcinomas of the cervix; indeed, p53 appears to be more frequently mutated in HPV-negative tumours

    Role of HPV: types 16 and 18 are associated with about 70% of cervical carcinomas (other high-risk types include 31, 33, 35, 39, 51, 52, and 56); these high-risk types are often demonstrable in the moderate and severe stages of preinvasive malignancy (CIN II and III); in these lesions they are commonly situated extrachromosomally while in carcinomas they are integrated into chromosomes at random locations, where they undergo disruption of the HPV E2 viral transcriptional regulatory protein; integration may thereby provide a selective advantage resulting in uncontrolled cellular proliferation leading to aneuploidy;
    it has recently been shown that a single finding of HPV DNA in a Pap smear from healthy women confers an increased risk of future invasive carcinoma that is positive for the same type of virus. Another recent study suggests that integration of high-risk HPV DNA in cervical swabs or tissue removed from patients with CIN II or III strongly suggests that progression to carcinoma will occur

  • Bibliography

    Cytogenetics of carcinoma of the cervix uteri: a review.
    Atkin NB
    Cancer genetics and cytogenetics. 1997 ; 95 (1) : 33-39.
    PMID 9140451
     
    Cancer of the uterine cervix.
    Cannistra SA, Niloff JM
    The New England journal of medicine. 1996 ; 334 (16) : 1030-1038.
    PMID 8598842
     
    Prognostic value of genomic alterations in invasive cervical squamous cell carcinoma of clinical stage IB detected by comparative genomic hybridization.
    Dellas A, Torhorst J, Jiang F, Proffitt J, Schultheiss E, Holzgreve W, Sauter G, Mihatsch MJ, Moch H
    Cancer research. 1999 ; 59 (14) : 3475-3479.
    PMID 10416613
     
    Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix.
    Heselmeyer K, Schröck E, du Manoir S, Blegen H, Shah K, Steinbeck R, Auer G, Ried T
    Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (1) : 479-484.
    PMID 8552665
     
    Role of the human papillomaviruses in human cancer.
    Howley PM
    Cancer research. 1991 ; 51 (18 Suppl) : 5019s-5022s.
    PMID 1653110
     
    Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix.
    Kersemaekers AM, Hermans J, Fleuren GJ, van de Vijver MJ
    British journal of cancer. 1998 ; 77 (2) : 192-200.
    PMID 9460988
     
    Comparative genomic hybridization reveals a recurrent pattern of chromosomal aberrations in severe dysplasia/carcinoma in situ of the cervix and in advanced-stage cervical carcinoma.
    Kirchhoff M, Rose H, Petersen BL, Maahr J, Gerdes T, Lundsteen C, Bryndorf T, Kryger-Baggesen N, Christensen L, Engelholm SA, Philip J
    Genes, chromosomes & cancer. 1999 ; 24 (2) : 144-150.
    PMID 9885981
     
    Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes.
    Klaes R, Woerner SM, Ridder R, Wentzensen N, Duerst M, Schneider A, Lotz B, Melsheimer P, von Knebel Doeberitz M
    Cancer research. 1999 ; 59 (24) : 6132-6136.
    PMID 10626803
     
    The molecular genetics of cervical carcinoma.
    Lazo PA
    British journal of cancer. 1999 ; 80 (12) : 2008-2018.
    PMID 10471054
     
    Genetic deletion and human papillomavirus infection in cervical cancer: loss of heterozygosity sites at 3p and 5p are important genetic events.
    Mitra AB
    International journal of cancer. Journal international du cancer. 1999 ; 82 (3) : 322-324.
    PMID 10399946
     
    Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status.
    Mullokandov MR, Kholodilov NG, Atkin NB, Burk RD, Johnson AB, Klinger HP
    Cancer research. 1996 ; 56 (1) : 197-205.
    PMID 8548763
     
    Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.
    Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L
    Nature. 1998 ; 393 (6682) : 229-234.
    PMID 9607760
     
    Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung.
    Sugita M, Tanaka N, Davidson S, Sekiya S, Varella-Garcia M, West J, Drabkin HA, Gemmill RM
    Cancer genetics and cytogenetics. 2000 ; 117 (1) : 9-18.
    PMID 10700859
     
    The role of the E6-p53 interaction in the molecular pathogenesis of HPV.
    Thomas M, Pim D, Banks L
    Oncogene. 1999 ; 18 (53) : 7690-7700.
    PMID 10618709
     
    Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer.
    Wallin KL, Wiklund F, Angström T, Bergman F, Stendahl U, Wadell G, Hallmans G, Dillner J
    The New England journal of medicine. 1999 ; 341 (22) : 1633-1638.
    PMID 10572150
     

    Citation

    This paper should be referenced as such :
    Atkin, NB
    Uterus: Carcinoma of the cervix
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):142-144.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/CervixUteriID5046.html
    History of this paper:
    Atkin, NB. Uterus: Carcinoma of the cervix. Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):162-163.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37546/09-1999-CervixUteriID5046.pdf


    Other genes implicated (Data extracted from papers in the Atlas) [ 174 ]

    Genes AAMP ADAMTS12 ANG ANXA1 APAF1 ARID1A AXIN1 BAK1 CCND1 BCL2L14
    BCL2L1 BIRC6 BLCAP BMP4 BRCA1 TIGAR CASZ1 CCNA1 CCNB1 CD44
    CDC20 CDC6 AGAP2 CFLAR CHD6 CKS2 CLDN7 CLSPN CRTC2 CSF1R
    CST6 CTDSPL CTHRC1 CTSB CTSH CXCL17 CYLD DAB2 DAPK1 DDIT4
    DIABLO DKK3 DLC1 DLG1 DNMT1 DYRK1A E2F1 ECT2 EDIL3 EEF1A1
    EFEMP1 EGR1 EIF3A EIF4E ENAH ENOX2 EPHA2 ERBB2 EYA2 FAM107B
    FAT1 FSCN1 GGH GLS2 GSDMB HDAC2 HIPK2 HOXC8 HSPB8 HSPD1
    HTRA1 HTRA3 IDO1 IL17A IL1RN INPPL1 IRF1 ITGA9 KCNH1 KDR
    KLK7 KLK8 KPNB1 LATS1 LDOC1 LOX LOXL2 LPAR2 LRIG1 MAL
    MAP3K7 MCM3 MCM5 KITLG MIR126 MIR133B MIR135A1 MIR143 MIR150 MIR211
    MIR22 MIR744 MIR125B1 MIR125B2 MKI67 MUC6 MYC MYLK NACC1 NANOG
    NCR2 NDUFA13 NOL3 NOTCH1 NR3C1 NR3C2 OPCML EP300 TP53
    PRKN PARK7 PDCD5 PEG3 PERP PIWIL1 PIWIL2 PKM PLAUR POU4F1
    PTGS2 PTK2 PTPRR RAB31 RAN RHOA ROBO1 ROCK2 S100P SLC16A1
    SLC16A3 SLC39A6 SLPI SMAD2 SMYD3 SNAI1 SNCG SPP1 SRSF1
    SRSF3 MMP11 ST6GALNAC1 STAT5B STEAP1 STK11 STMN1 TBX3 TGFBR2 THBS2
    TMSB10 TPBG TPX2 TRIO TRPV1 TSPAN1 TWIST1 TWIST2 TXN UBE3A
    USP15 USP7 WIF1 XPO1

    External links

    arrayMap Topo ( C53) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
     
     
    Other databaseICGC Data Portal - [UCEC-US] Uterine Corpus Endometrial Carcinoma- TCGA, US
    Other databaseCervical and endocervical cancers (CESC) TCGA Copy Number Portal
    Other databaseCervical Cancer Overview - Disease Synopsis [canSAR]
    Other databaseCervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma [ Genomic Data Commons - NCI TCGA-CESC]
    Disease databaseUterus: Carcinoma of the cervix
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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    indexed on : Tue Sep 26 12:36:58 CEST 2017


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