Aims-Microsatellite instability (MSI) was first observed in hereditary non-
polyposis colorectal carcinoma (HNPCC) and was subsequently seen in non-fam
ilial colorectal carcinoma. The relation between MSI and cancer associated
genes in nonfamilial colorectal carcinomas has yet to be evaluated. To clar
ify this matter, changes in cancer associated genes were examined in non-fa
milial colorectal carcinomas.
Methods-Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ra
s genes were analysed in 24 MSI high (alterations in four to seven of seven
loci), nine MSI low (alterations in one to three of seven loci), and 31 MS
I negative non-familial carcinomas. The hMSH2 and hMLH1 genes were also ana
lysed in 24 MSI high carcinomas.
Results-Both the frequencies and types of alterations in the APC and p53 ge
nes in MSI high carcinomas were the same as those in MSI low and MSI negati
ve carcinomas; however, they were different from those seen in HNPCC. The f
requency of Ki-ras mutation was significantly lower in the MSI high cases (
two of 24; 8%) than in the others (15 of 38; 39%). Somatic mutation of hMSH
2 or hMLH1 was detected in six of 24 (25%) of the MSI high cases.
Conclusions-These results suggest that APC and p53 alterations occur irresp
ective of microsatellite instability status in non-familial colorectal carc
inomas, and that Ki-ras mutation is not involved in MSI high non-familial c
olorectal carcinoma. The pathogenesis of these carcinomas may differ from b
oth the usual adenoma-carcinoma sequence and HNPCC carcinogenesis.