Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Sep;89(9):895–902. doi: 10.1111/j.1349-7006.1998.tb00646.x

Association of Replication Error Positive Phenotype with Lymphocyte Infiltration in Endometrial Cancers

Toshimasa Kihana 1,3,, Toru Fujioka 1, Katsuyuki Hamada 1, Katsumi Kito 2, Akira Takahashi 4, Choutatsu Tsukayama 5, Masaharu Ito 1
PMCID: PMC5921952  PMID: 9818024

Abstract

Microsatellite instability (MI) has been detected in certain sporadic cancers as well as in hereditary non‐polyposis colorectal cancer (HNPCC). In order to determine the precise clinicopathological characteristics of MI in endometrial cancer, we examined 90 sporadic endometrial cancers (83 endometrioid adenocarcinomas, 3 adenosquamous carcinomas, 3 papillary serous carcinomas, and 1 clear cell carcinoma) and eight lesions of endometrial hyperplasia for replication error (RER) using polymerase chain reaction amplification of CA repeated microsatellite sequences at 15 loci. RER was observed in 23 (28%) of the 83 endometrioid adenocarcinomas at at least one locus and in 19 (23%) at two or more loci (RER+ phenotype) in the seven most commonly observed loci, but not in carcinomas of other histological types or in endometrial hyperplasia. Lymphocyte infiltration around carcinoma cells, which is one of the histological features seen in tumors from HNPCC, was severer in RER+ phenotype tumors (79%, 11/14) than in the RER– tumors (25%, 11/44) (marked/moderate infiltration versus slight, P<0.001, χ2 test), when 58 tumors with muscular invasion were examined. The RER+ phenotype was associated with a higher parity and gravidity (P<0.05, Wilcoxon test). However, RER+ phenotype was not associated with tumor stage, histological grade, muscular invasion, lymph node metastasis or patient survival. In conclusion, MI occurs in a subset of endometrial cancers, which often show marked infiltration of lymphocytes around the tumor.

Keywords: key words, Microsatellite instability, Replication error, Endometrial cancer, Clinicopathological characteristics, Lymphocyte accumulation

Full Text

The Full Text of this article is available as a PDF (891.3 KB).

REFERENCES

  • 1. ) Fearon , E. R. and Vogelstein , B.A genetic model for colorectal carcinogenesis . Cell , 61 , 759 – 767 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Lynch , H. T. and Smyrk , T.Hereditary nonpolyposis colorectal cancer (Lynch syndrome) . Cancer , 78 , 1149 – 1167 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Liu , B. , Nicolaides , N. C. , Markowitz , S. , Willson , J. K. V. , Parsons , R. E. , Jen , J. , Papadopolous , N. , Peltomaki , P. , de la Chapelle , A. , Hamilton , S. R. , Kinzler , K. W. and Vogelstein , B.Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability . Nat. Genet. , 9 , 48 – 55 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Markowitz , S. , Wang , J. , Myeroff , L. , Parsons , R. , Sun , L. , Lutterbagh , J. , Fan , R. S. , Zborowska , E. , Kinzler , K. W. , Vogelstein , B. , Brattain , M. and Willson , J. K. V.Inactivation of the type II TGF‐β receptor in colon cancer cells with microsatellite instability . Science , 268 , 1336 – 1338 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Bodmer , W. , Bishop , T. and Karran , P.Genetic steps in colorectal cancer . Nat. Genet. , 6 , 217 – 219 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Peltomaki , P. , Lothe , R. A. , Aaltonen , L. A. , Pylkkanen , L. , Nystrom‐Lahti , M. , Seruca , R. , David , L. , Holm , R. , Ryberg , D. , Haugen , A. , Brogger , A. , Borresen , A.‐L. and de la Chapelle , A.Microsatellite instability is associated with tumors that characterize the hereditary non‐polyposis colorectal carcinoma syndrome . Cancer Res. , 53 , 5853 – 5955 ( 1993. ). [PubMed] [Google Scholar]
  • 7. ) Risinger , J. I. , Berchuck , A. , Kohler , M. F. , Watson , P. , Lynch , H. T. and Boyd , J.Genetic instability of microsatellite in endometrial carcinoma . Cancer Res. , 53 , 5100 – 5103 ( 1993. ). [PubMed] [Google Scholar]
  • 8. ) Burks , R. T. , Kessis , T. D. , Cho , K. R. and Hedrick , L.Microsatellite instability in endometrial cancer . Oncogene , 9 , 1163 – 1166 ( 1994. ). [PubMed] [Google Scholar]
  • 9. ) Duggan , B. D. , Felix , J. C. , Muderspach , L. I. , Tourgeman , D. , Zheng , J. and Shibata , D.Microsatellite instability in sporadic endometrial carcinoma . J. Natl. Cancer Inst. , 86 , 1216 – 1221 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Kobayashi , K. , Sagae , S. , Kudo , R. , Saito , H. , Koi , S. and Nakamura , Y.Microsatellite instability in endometrial carcinomas: frequent replication errors in tumors of early onset and/or of poorly differentiated type . Genes Chromosom. Cancer , 14 , 128 – 132 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Lothe , R. A. , Peltomaki , P. , Meling , G. I. , Aaltonen , L. A. , Nystrom‐Lahti , M. , Pylkkanen , L. , Heimdal , K. , Andersen , T. I. , Moller , P. , Rognum , T. O. , Fossa , S. D. , Haldorsen , T. , Langmark , F. , Brogger , A. , de la Chapelle , A. and Borresen , A.‐L.Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history . Cancer Res. , 53 , 5849 – 5852 ( 1993. ). [PubMed] [Google Scholar]
  • 12. ) Kihana , T. , Tsuda , H. , Teshima , S. , Nomoto , K. , Tsugane , S. , Sonoda , T. , Matsuura , S. and Hirohashi , S.Prognostic significance of the overexpression of c‐erbB‐2 protein in adenocarcinoma of the uterine cervix . Cancer , 73 , 148 – 153 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Creasman , W. T.Announcement, FIGO stages: 1988 Revisions . Gynecol. Oncol. , 35 , 125 – 127 ( 1989. ). [Google Scholar]
  • 14. ) Poulsen , C. E. , Taylor , C. W. and Sobin , L. H.Histological typing of female genital tract tumors . In “International Histological Classification of Tumors,” No. 13 ( 1975. ). World Health Organization; , Geneva . [Google Scholar]
  • 15. ) Hendrickson , M. , Ross , J. , Eifel , P. , Martinez , A. and Kempson , R.Uterine papillary serous carcinoma: a highly malignant form of endometrial carcinoma . Am. J. Surg. Pathol. , 6 , 93 – 108 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Jones , M. H. and Nakamura , Y.Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism . Genes Chromosom. Cancer , 5 , 89 – 90 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Hall , J. M. , Friedman , L. , Guenther , C. , Lee , M. K. , Weber , J. L. , Black , D. M. and King , M.‐C.Closing in on a breast cancer gene on chromosome 17q . Am. J. Hum. Genet. , 50 , 1235 – 1242 ( 1992. ). [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Risinger , J. I. and Boyd , J.Dinucleotide repeat polymorphism in the human DCC gene at chromosome 18q21 . Hum. Mol. Genet. , 1 , 656 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Kozman , H. M. , Keith , T. P. , Donis‐Keller , H. , White , R. L. , Weissenbach , J. , Dean , M. , Vegnaud , G. , Kidd , K. , Gusella , J. , Royle , N. J. , Sutherland , G. R. and Mulley , J. C.The CEPH consortium linkage map of human chromosome 16 . Genomics , 25 , 44 – 58 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Kihana , T. , Yano , N. , Murao , S. , Iketani , H. , Hamada , K. , Yano , J. and Matsuura , S.Allelic loss of chromosome 16q in endometrial cancer: correlation with poor prognosis of patients and less differentiated histology . Jpn. J. Cancer Res. , 87 , 1184 – 1190 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. ) Myeroff , L. L. , Parsons , R. , Kim , S.‐J. , Hedrick , L. , Cho , K. R. , Orth , K. , Mathis , M. , Kinzler , K. W. , Lutterbagh , J. , Park , K. , Bang , Y.‐J. , Lee , H. Y. , Park , J. G. , Lynch , H. T. , Roberts , A. B. , Vogelstein , B. and Markowitz , S. D.A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability . Cancer Res. , 55 , 5545 – 5547 ( 1995. ). [PubMed] [Google Scholar]
  • 22. ) Suzuki , Y. , Sekiya , T. and Hayashi , K.Allele‐specific polymerase chain reaction: a method for amplification and sequence determination of a single component among a mixture of sequence variants . Anal. Biochem. , 192 , 82 – 84 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Han , H.‐J. , Yanagisawa , A. , Kato , Y. , Park , J.‐G. and Nakamura , Y.Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer . Cancer Res. , 53 , 5087 – 5089 ( 1993. ). [PubMed] [Google Scholar]
  • 24. ) Jovanovic , A. S. , Boynton , K. A. and Mutter , G. L.Uteri of woman with endometrial carcinoma contain a histopathological spectrum of monoclonal putative precancer, some with microsatellite instability . Cancer Res. , 56 , 1917 – 1921 ( 1995. ). [PubMed] [Google Scholar]
  • 25. ) Kim , H. , Jen , J. , Vogelstein , B. and Hamilton , R.Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences . Am. J. Pathol. , 145 , 148 – 156 ( 1994. ). [PMC free article] [PubMed] [Google Scholar]
  • 26. ) Seruca , R. , Santos , N. R. , David , L. , Constancia , M. , Barroca , H. , Carneiro , F. , Seixas , M. , Peltomaki , P. , Lothe , R. and Sobrinho‐Simoes , M.Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathological profile . Int. J. Cancer , 64 , 32 – 36 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Bicknell , D. C. , Rowan , A. and Bodmer , W. F.β2‐Microglobulin gene mutations: a study of established colorectal cell lines and fresh tumors . Proc. Natl. Acad. Sci. USA , 91 , 4751 – 4755 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Kihana , T. , Hamada , K. , Inoue , Y. , Yano , N. , Iketani , H. , Murao , S. , Ukita , M. and Matsuura , S.Mutation and allelic loss of the p53 gene in endometrial carcinoma: incidence and outcome in 92 surgical patients . Cancer , 76 , 72 – 78 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Horii , A. , Han , H.‐J. , Shimada , M. , Yanagisawa , A. , Kato , Y. , Ohta , H. , Yasui , W. , Tahara , E. and Nakamura , Y.Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancer . Cancer Res. , 54 , 3373 – 3375 ( 1994. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES