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Geno- and pheno-typic characterization in ten patients with double-primary gastric and colorectal adenocarcinomas

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Although a number of double-primary gastric and colorectal cancers have been known to correlate with the mutator pathway, a possible association with known hereditary cancers regarding geno-pathogenesis has rarely been investigated. This study was intended to identify a possible association of hereditary cancers and the implications of the mutator or tumor-suppressor pathway in double-primary gastric and colorectal cancers.

Materials and methods

Fresh colorectal tissues and lymphocytes from ten patients with double-primary gastric and colorectal cancers were obtained consecutively. The mutator pathway was evaluated by detecting hMSH2 and hMLH1 mutations, microsatellite instability (MSI) using 12 microsatellite markers, and hMLH1 promoter region methylation. Protein expressions of hMSH2, hMLH1, APC, E-cadherin, and β-catenin were identified by immune staining.

Results

There was no pathogenic mutation in any introns or exons of hMSH2, hMLH1 or CDH1, and in exons 3, 5, 6, and 15 of CTNNB1. Either MSI or methylator phenotype was found in five gastric cancers and in four colorectal cancers. No patients met the Amsterdam criteria of hereditary nonpolyposis colorectal cancer (HNPCC) or its equivalent of hereditary gastric cancer. Two patients with gastric cancers among their first-degree relatives showed no E-cadherin expression. The two of the three patients with rectal cancers among their first-degree relatives showed mutator phenotype either in the gastric or in the colorectal cancer. A subset of double-primary gastric and colorectal cancers may thereby be categorized as variant forms of hereditary gastric or colorectal cancer. Both cytoplasmic and nuclear β-catenins were expressed in all gastric and colorectal cancers. Among the gastric and colorectal cancers with either MSI or methylator phenotype, four of five gastric cancers showed both APC and E-cadherin expression, whereas one of four colorectal cancers showed them.

Conclusion

This may suggest that the mutator pathway and the aberrant tumor suppressor pathway of the APC-E-cadherin may be cooperative or separately activated in the geno-pathogenesis of double-primary gastric and colorectal cancers.

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Acknowledgments

This study was supported by Asan grant 2002/3-069, Seoul, Korea. The authors gratefully acknowledge Prof. Walter F. Bodmer (Hertford College, University of Oxford, Oxford, UK) for his highly valuable discussion and Bonnie Hami, M.A., (University Hospital of Cleveland, Cleveland, OH) for her editorial assistance.

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Authors and Affiliations

  1. Department of Surgery, University of Ulsan College of Medicine and Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, 388-1 Poongnap-2-Dong Songpa-Ku, 138-736, Seoul, Korea

    Jin C. Kim, Kum H. Koo & Hee C. Kim

  2. Department of Pathology, University of Ulsan College of Medicine, 388-1 Poongnap-2-Dong Songpa-Ku, 138-736, Seoul, Korea

    Jung S. Kim

  3. Department of Pathology, College of Medicine, Seoul National University, 28 Yeongeon-Dong Jongro-Ku, 110-744, Seoul, Korea

    Gyeong H. Kang

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  1. Jin C. Kim
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Correspondence to Jin C. Kim.

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Kim, J.C., Koo, K.H., Kim, H.C. et al. Geno- and pheno-typic characterization in ten patients with double-primary gastric and colorectal adenocarcinomas. Int J Colorectal Dis 19, 561–568 (2004). https://doi.org/10.1007/s00384-004-0591-7

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