MICROSATELLITE INSTABILITY IN YOUNG-PATIENTS WITH COLORECTAL-CANCER

Genetic instability is closely correlated to the pathogenesis of hered itary non-polyposis colon cancer (HNPCC), which is clinically characte rized by a family history and early onset. To investigate the role of genetic instability in young patients with colorectal cancer (CRC), 22 CRC patients, who were aged younger than 30 at the time of diagnosis, were studied. Patients with familial adenomatous polyposis were exclu ded. Among the 22 cases, seven were identified as microsatellite insta bility positive (MI+), and more than five microsatellite markers among the 15 tested markers showed an additional band pattern in the tumor tissue. None of the remaining 15 cases showed instability In any micro satellite marker. Two of seven MI+ cases were classic HNPCC. While all MI+ cases had one or no metastatic lymph node, 53.3% of MI- cases sho wed metastasis in two or more regional lymph nodes. Allelic deletion o f the 17p12-13 chromosome around the p53 locus occurred in 16.7% of MI + cases, and 80.0% of MI- cases showed loss of heterozygosity at that locus. hMSH2 Protein expression, assessed by immunohistochemistry, was absent in two cases, both of which were MI+. When we tested two to fo ur sites of MI+ tumors, transforming growth factor beta receptor type II was mutated in a homogeneous pattern in five Mit cases. In addition , frame-shift mutations of BAX, insulin-like growth factor II receptor , hMSH3 and hMSH6 were found in three cases, five cases, five cases an d one case, respectively. In contrast to the consistent mutation of th e transforming growth factor-beta receptor type II gene, mutations of other genes varied in different portions of the tumors.