Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability

Citation
K. Shitoh et al., Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability, J CLIN PATH, 53(11), 2000, pp. 841-845
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF CLINICAL PATHOLOGY
ISSN journal
0021-9746 → ACNP
Volume
53
Issue
11
Year of publication
2000
Pages
841 - 845
Database
ISI
SICI code
0021-9746(200011)53:11<841:PONCCW>2.0.ZU;2-Q
Abstract
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.