Differences In Characteristics Of Colon Tumors Between Hereditary Nonpolyposis Colon Cancer, Familial Polyposis And Sporadic Cases

To clarify the nature of HNPCC tumors, RER and genetic changes were compared between HNPCC and non-HNPCC tumors. In HNPCC 95% tumors at all stages exhibited RER(+) (altered loci:4.3 of 5). In FAP and sporadic tumors RER(+) (1.7 of 5) was 3% in adenoma and intramucosal carcinoma, 13% to 24% in invasive carcinoma, and 35% in carcinoma metastasized to liver. Fifty % of RER(+) HNPCC tumors exhibited both germ-line and somatic mutations of hMSH2 or hMLH1 gene, whereas 6% of RER(+) non-HNPCC had somatic mutation. Frequencies of APC, p53 and Kras-2 mutations and LOHs of tumor suppressor genes were significantly lower (P=0.03 to 0.0006), but TGF beta RII mutation was extremely higher (P=0.000001) in HNPCC than in non-HNPCC. These results suggest that RER(+) occurs from an early stage of carcinogenesis in HNPCC but later stages in non-HNPCC and most HNPCC tumors may develop through different genetic changes from those in adenoma-carcinoma sequence, although a certain percentage develop through APC mutation.