Geno- and pheno-typic characterization in ten patients with double-primary gastric and colorectal adenocarcinomas
Autor: | Jung S. Kim, Hee C. Kim, Gyeong Hoon Kang, Kum H. Koo, Jin C. Kim |
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Rok vydání: | 2004 |
Předmět: |
Male
medicine.medical_specialty Genes APC Genotype Colorectal cancer DNA Mutational Analysis Molecular Sequence Data Adenocarcinoma Gastroenterology Pathogenesis Gastric adenocarcinoma Stomach Neoplasms Internal medicine medicine Humans Stomach cancer Colonic disease Aged Aged 80 and over Base Sequence business.industry Neoplasms Second Primary Middle Aged Hepatology Cadherins medicine.disease Pedigree Cell Transformation Neoplastic Phenotype Cancer research Female Colorectal Neoplasms business Rectal disease |
Zdroj: | International Journal of Colorectal Disease. 19:561-568 |
ISSN: | 1432-1262 0179-1958 |
DOI: | 10.1007/s00384-004-0591-7 |
Popis: | 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.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 beta-catenin were identified by immune staining.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 beta-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.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. |
Databáze: | OpenAIRE |
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