Advertisement
Original articles| Volume 114, ISSUE 2, P130-135, October 15, 1999

Download started.

Ok

DNA Replication Error in Endometrial Carcinoma and Complex Atypical Endometrial Hyperplasia

      Abstract

      We attempted to define the relation between DNA replication errors (RERs) in endometrial carcinomas and the precancerous lesion complex atypical endometrial hyperplasia (ATH) and clinicopathological characteristics. Tissue samples from 93 patients with endometrial carcinoma diagnosed as endometrioid adenocarcinoma and 26 patients with ATH (including 21 in whom endometrial carcinoma also was found) were prepared as formalin-fixed, paraffin-embedded sections. The samples were examined for the presence of RERs by the polymerase chain reaction with the use of five microsatellite markers. RERs were observed at 1 loci in 32 endometrial carcinoma patients (34%); all 26 ATH patients were RER negative. RERs were observed in 25% of stage I and stage II cancer patients (16/64) and in 55% of stage III and stage IV cancer patients (16/29) (P = 0.009), as well as in 63% (10/16) of cancer patients with and in 27% (20/75) of patients without lymph-node metastases (P = 0.013). The incidence of RERs was not related to patient age, histological tumor grade, or prognosis. These results suggest that RER may be involved in the advanced rather than the early stages of endometrioid adenocarcinoma. There appears to be little association between RER and ATH.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Aaltonen L.A.
        • Peltomäki P.
        • Leach F.S.
        • Sistonen P.
        • Pylkkänen L.
        • Mecklin J.-P.
        • Järvinen H.
        • Powell S.M.
        • Jen J.
        • Hamilton S.R.
        • Petersen G.M.
        • Kinzler K.W.
        • Vogelstein B.
        • de la Chapelle A.
        Clues to the pathogenesis of familial colorectal cancer.
        Science. 1993; 260: 812-816
        • Aaltonen L.A.
        • Peltomäki P.
        • Mecklin J.-P.
        • Järvinen H.
        • Jass J.R.
        • Green J.S.
        • Lynch H.T.
        • Watson P.
        • Tallqvist G.
        • Juhola M.
        • Sistonen P.
        • Hamilton S.R.
        • Kinzler K.W.
        • Vogelstein B.
        • de la Chapelle A.
        Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients.
        Cancer Res. 1994; 54: 645-1648
        • Jacoby R.F.
        • Marshall D.J.
        • Kailas S.
        • Schlack S.
        • Harm B.
        • Lov R.
        Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer.
        Gastroenterology. 1995; 109: 73-82
        • Fishel R.
        • Lescoe M.K.
        • Rao M.R.S.
        • Copelan N.G.
        • Jenkins N.A.
        • Garber J.
        • Kane M.
        • Kolodner R.
        The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
        Cell. 1993; 75: 1027-1038
        • Leach F.S.
        • Nicolaides N.C.
        • Papadopoulos N.
        • Liu B.
        • Jen J.
        • Parsons R.
        • Peltomäki P.
        • Sistonen P.
        • Aaltonen L.A.
        • Nyström-Lahti M.
        • Guan X.-Y.
        • Zhan J.
        • Meltzer P.S.
        • Yu J.-W.
        • Kao F.-T.
        • Chen D.J.
        • Cerosaletti K.M.
        • Fournier R.E.K.
        • Todd S.
        • Lewis T.
        • Leach R.J.
        • Naylor S.L.
        • Weissenbach J.
        • Mecklin J.-P.
        • Järvinen H.
        • Petersen G.M.
        • Hamilton S.R.
        • Green J.
        • Jass J.
        • Watson P.
        • Lynch H.T.
        • Trent J.M.
        • de la Chapelle A.
        • Kinzler K.W.
        • Vogelstein B.
        Mutations of a mut S homolog in hereditary nonpolyposis colorectal cancer.
        Cell. 1993; 75: 1215-1225
        • Papadopoulos N.
        • Nicolaides N.C.
        • Wei Y.-F.
        • Ruben S.M.
        • Carter K.C.
        • Rosen C.A.
        • Haseltine W.A.
        • Fleischmann R.D.
        • Fraser C.M.
        • Adams M.D.
        • Venter J.C.
        • Hamilton S.R.
        • Petersen G.M.
        • Watson P.
        • Lynch H.T.
        • Peltömaki P.
        • Mecklin J.-P.
        • de la Chapelle A.
        • Kinzler K.W.
        • Vogelstein B.
        Mutation of a mut L homolog in hereditary colon cancer.
        Science. 1994; 263: 1625-1629
        • Bronner C.E.
        • Baker S.M.
        • Morrison P.T.
        • Warren G.
        • Smith L.G.
        • Lescoe M.K.
        • Kane M.
        • Earabino C.
        • Lipford J.
        • Lindblom A.
        • Tannergard P.
        • Bollag R.J.
        • Godwin A.R.
        • Ward D.C.
        • Nordenskjld M.
        • Fishel R.
        • Kolodner R.
        • Liskay R.M.
        Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer.
        Nature. 1994; 368: 258-261
        • Nicolaides N.C.
        • Papadopoulos N.
        • Lin B.
        • Wei Y.-E.
        • Carter K.C.
        • Ruben S.M.
        • Rosen C.A.
        • Haseltine W.A.
        • Fleischmann D.
        • Fraser C.M.
        • Adams M.D.
        • Venter J.C.
        • Dunlo M.G.
        • Hamilton S.R.
        • Petersen G.M.
        • de la Chapelle A.
        • Vogelstein B.
        • Kinzler K.W.
        Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.
        Nature. 1994; 371: 75-80
        • Risinger J.I.
        • Berchuck A.
        • Kohle M.E.
        • Watson P.
        • Lynch H.T.
        • Boyd J.
        Genetic instability of microsatellites in endometrial carcinoma.
        Cancer Res. 1993; 53: 5100-5103
        • Duggan B.D.
        • Felix J.C.
        • Muderspach L.I.
        • Tourgeman D.
        • Zheng J.
        • Shibata D.
        Microsatellite instability in sporadic endometrial carcinoma.
        J Natl Cancer Inst. 1994; 86: 1216-1220
        • Kobayashi K.
        • Sagae S.
        • Kudo R.
        • Saito H.
        • Koi S.
        • Nakamura Y.
        Microsatellite instability in endometrial carcinomas.
        Genes Chromosom Cancer. 1995; 14: 128-132
        • Burks R.T.
        • Kessis T.D.
        • Cho K.R.
        • Hedrick L.
        Microsatellite instability in endometrial carcinoma.
        Oncogene. 1994; 9: 1163-1166
        • Caduff R.F.
        • Johnston C.M.
        • Svoboda-Newman S.M.
        • Poy E.
        • Merajver S.D.
        • Frank T.S.
        Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma.
        Am J Pathol. 1996; 148: 1671-1678
        • Kurman R.J.
        • Norris H.J.
        Endometrial hyperplasia and related cellular changes.
        in: Kurman R.J. Blaustein's Pathology of the Female Genital Tract. ed 4. Springer, New York1994: 411-437
        • Wright D.K.
        • Manos M.M.
        Sample preparation from paraffin-embedded tissues.
        in: Innis M.A. Gelfand D.H. White T.J. PCR Protocols A Guide to Methods and Applications. Academic Press, New York1990: 153-158
        • Jones M.H.
        • Nakamura Y.
        Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism.
        Genes Chromosom Cancer. 1992; 5: 89-90
        • Gyapay G.
        • Morissette J.
        • Vignal A.
        • Dib C.
        • Fizames C.
        • Millasseau P.
        • Marc S.
        • Bemardi G.
        • Lathro M.
        • Weissenbach J.
        The 1993-94 Généthon human genetic linkage map.
        Nat Genet. 1994; 7: 246-339
        • Jones M.H.
        • Yamakawa K.
        • Nakamura Y.
        Isolation and characterization of 19 dinucleotide repeat polymorphisms on chromosome 3p.
        Hum Mol Genet. 1992; 1: 131-133
        • Senba S.
        • Konishi F.
        • Okamoto T.
        • Kashiwagi H.
        • Kanazawa K.
        • Miyaki M.
        • Konishi M.
        • Tsukamoto T.
        Clinicopathologic and genetic features of non-familial colorectal carcinomas with a DNA replication error.
        Cancer. 1998; 82: 279-285
        • Kaplan E.L.
        • Meier P.
        Nonparametric estimation for incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Tashiro H.
        • Lax S.F.
        • Gaudin P.B.
        • Isacson C.
        • Cho K.R.
        • Hedrick L.
        Microsatellite instability is uncommon in uterine serous carcinoma.
        Am J Pathol. 1997; 150: 75-79
        • Akiyama Y.
        • Iwanaga R.
        • Saitoh K.
        • Shiba K.
        • Ushio K.
        • Ikeda E.
        • Iwama T.
        • Nomizu T.
        • Yuasa Y.
        Transforming growth factor β type II receptor gene mutations in adenomas from hereditary nonpolyposis colorectal cancer.
        Gastroenterology. 1997; 112: 33-39
        • Young J.
        • Leggett B.
        • Gustafson C.
        • Ward M.
        • Searle J.
        • Thomas L.
        • Buttenshaw R.
        • Chenevix-Trench G.
        Genomic instability occurs in colorectal carcinomas but not in adenomas.
        Hum Mutat. 1993; 2: 351-354
        • Thibodeau S.N.
        • Bren G.
        • Schaid D.
        Microsatellite instability in cancer of the proximal colon.
        Science. 1993; 260: 816-819
        • Mutter G.L.
        • Boynton K.A.
        • Faquin W.C.
        • Ruiz R.E.
        • Jovanovic A.S.
        Allelotype mapping of unstable microsatellites establishes direct lineage continuity between endometrial precancers and cancer.
        Cancer Res. 1996; 56: 4483-4486