Microsatellite instability in young patients with colorectal cancer

Genetic instability Is closely correlated to the pathogenesis of hereditary non-palyposis colon cancer (HNPCC), which is clinicaily characterized by a family history and early onset. To investigate the role of genetic instabllity 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 famllial adenomatous polyposis were excluded. Among the 22 cases, seven were identifled as microsateillte instability posltive (MI+), and more than five microsatellite markers among the 15 tested markers showed an additlonal band pattern in the tumor tissue. None of the remaining 15 cases showed instability in any microsatellite 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 showed metastasls in two or more reglonal lymph nodes. Allelic deletion of the 17p12–13 chromosome around the p53 locus occurred in 16.7% of MI+ cases, and 80.0% of MI- cases showed loss of het-erozygosity at that locus. hMSH2 Protein expression, assessed by immunohistochemistry, was absent in two cases, both of which were MI+. When we tested two to four sites of MI+ tumors, transforming growth factor β receptor type II was mutated in a homogeneous pattern in five MI+ 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 and one case, respectively. In contrast to the consistent mutatlon of the transforming growth factor-β receptor type II gene, mutations of other genes varied in different portions of the tumors.