Abstract
Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K‐ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K‐ras. No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K‐ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.
Keywords: Mixed hyperplastic adenomatous polyp, Serrated adenoma, APC gene, K‐ras gene, p53 gene
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REFERENCES
- 1. ) Hamilton , S. R.The molecular genetics of colorectal neoplasia . Gastroenterology , 105 , 3 – 7 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Jacoby , R. F. , Marshall , D. J. , Kailas , S. , Schlack , S. , Harms , B. and Love , R.Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer . Gastroenterology , 109 , 73 – 82 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Allen , J. I.Molecular biology of colorectal cancer: a clinician's view . Prospect Colon Rectal Surg. , 8 , 181 – 202 ( 1995. ). [Google Scholar]
- 4. ) Miyoshi , Y. , Nagase , H. , Ando , H. , Horii , A. , Ichii , A. , Nakatsuru , S. , Aoki , T. , Miki , Y. , Mori , T. and Nakamura , Y.Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene . Hum. Mol. Genet. , 4 , 229 – 233 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Jen , J. , Powell , S. M. , Papadopoulos , N. , Smith , K. J. , Hamilton , S. R. , Vogelstein , B. and Kinzler , K. W.Molecular determinants of dysplasia in colorectal lesions . Cancer Res. , 54 , 5523 – 5526 ( 1994. ). [PubMed] [Google Scholar]
- 6. ) Longacre , T. A. and Fenoglio‐Preiser , C. M.Mixed hyperplastic adenomatous polyps/serrated adenomas . Am. J. Surg. Pathol. , 14 , 524 – 537 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Jeevaratnam , P. , Cottier , D. S. , Browett , P. J. , van De Water , N. S. , Pokos , V. and Jass , J. R.Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome . J. Pathol. , 179 , 20 – 25 ( 1996. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Torlakovic , E. and Snover , D. C.Reevaluating hyperplastic polyposis: a new entity discovered . Colon Rectal Surg. Outlook , 9 ( 7 ), 1 – 2 ( 1996. ). [Google Scholar]
- 9. ) Brown , D. C. and Gatter , K. C.Monoclonal antibody Ki‐67: its use in histopathology . Histopathology , 17 , 489 – 503 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Johnston , P. G. , O'Brien , M. J. , Dervan , P. A. and Carney , D. N.Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa . Hum. Pathol. , 20 , 696 – 700 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Strenberger , L. A. , Hardy , P. H. , Cuculis , J. J. and Meyer , H. G.The unlabeled antibody‐enzyme method of immunohistochemistry. Preparation and properties of soluble antigen‐antibody complex (horseradish peroxidase anti‐horseradish peroxidase) and its use in identification of spirochetes . J. Histochem. Cytochem. , 18 , 315 – 333 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Sato , T. , Tanigami , A. , Yamakawa , K. , Akiyama , F. , Kasumi , F. , Sakamoto , G. and Nakamura , Y.Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer . Cancer Res. , 50 , 7184 – 7189 ( 1990. ). [PubMed] [Google Scholar]
- 13. ) Goelz , S. E. , Hamilton , S. R. and Vogelstein , B.Purification of DNA from formaldehyde‐fixed and paraffin‐embedded human tissue . Biochem. Biophys. Res. Commun. , 130 , 118 – 126 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Spirio , L. , Joslyn , G. , Nelson , L. , Leppert , M. and White , R.A CA repeat 30–70 KB downstream from the adenomatous polyposis coli (APC) gene . Nucleic Acids Res. , 19 , 6348 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Wijnen , J. , Tops , C. , Breukel , C. , Leeuwen , C. V. , Goverde , A. , van Der Kliff , H. , Fodde , R. and Khan , P. M.CA repeat polymorphism from YAC JW25 at the D5S318 locus, distal to adenomatous polyposis coli (APC) . Nucleic Acids Res. , 19 , 6965 ( 1991. ). [DOI] [PMC free article] [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. ) Miyaki , M. , Konishi , M. , Kikuchi Yanoshita , R. , Enomoto , M. , Igari , T. , Tanaka , K. , Muraoka , M. , Takahashi , H. , Amada , Y. , Fukayama , M. , Maeda , Y. , Iwama , T. , Mishima , Y. , Mori , T. and Koike , M.Characteristics of somatic mutation of adenomatous polyposis coli gene in colorectal tumors . Cancer Res. , 54 , 3011 – 3020 ( 1994. ). [PubMed] [Google Scholar]
- 18. ) Vogelstein , B. , Fearon , E. R. , Hamilton , S. R. , Kern , S. E. , Preisinger , A. C. , Leppert , M. , Nakamura , Y. , White , R. , Smits , A. M. M. and Bos , J. L.Genetic alterations during colorectal‐tumor development . N. Engl. J. Med. , 319 , 525 – 532 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Urbanski , S. J. , Marcon , N. , Kossakowska , A. E. and Bruce , W. R.Mixed hyperplastic adenomatous polyps—an underdiagnosed entity . Am. J. Surg. Pathol. , 8 , 551 – 556 ( 1984. ). [PubMed] [Google Scholar]