Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring-cell carcinoma of colorectum

In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet- ring-cell carcinomas (sig) of the colorectum, K-ras gene mutation, p53 immu nostaining and microsatellite instability (MSI) were analyzed for a compari son with 46 cases of colorectal carcinomas of the well or moderately differ entiated type (well/mod). In addition, the mutations of simple repeated seq uences in the transforming-growth-factor-beta type-II receptor (T beta R-II ) gene and the BAX gene were analyzed as possible targets for DNA replicati on errors. Mutation of the K-ras gene in the per, sig and well/mod specimen s was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift m utation of the T beta R-II gene was detected in 27.5% of the por and none o f the sig specimens, while corresponding figures for mutation of the BAX ge ne were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K-ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumor's location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T beta R-II or the BAX gene was found. These results suggest that poorly different iated and signet-ring-cell carcinomas have a genetic background different f rom that of well or moderately differentiated carcinomas of the colorectum, and that DNA-replication error is at least partly involved in the carcinog enesis of these specific types of colorectal carcinomas. (C) 1999 Wiley-Lis s, Inc.