Correlation of genetic instability with mismatch repair protein expressionand p53 mutations in non-small cell lung cancer

To examine the etiological association of genetic instability in lung tumor igenesis, we investigated the frequency of microsatellite instability (MI) of eight dinucleotide repeat markers in 68 patients with non-small cell lun g cancer. Twenty-eight patients (41.2%) evidenced instability in multiple t ested microsatellite markers ranging from 3-7 and were defined as MI-positi ve patients, MI occurred more frequently in patients suffering from squamou s cell lung carcinoma (P = 0.004). We examined the association between MI a nd expression of hMLH1 mismatch repair protein by immunohistochemical analy sis of hMLH1 protein in paraffin-embedded tumors from 64 patients, Twenty M I-positive patients (76.9%) had no expression of hMLH1 protein. The data sh owed that hn was associated with altered hMLH1 expression (P = 0.03). To ex amine the role of genetic instability in the previous identified small intr agenic deletion of the p53 gene, we explored the association between MI and p53 gene mutations. All patients, except one, containing small intragenic deletion in p53 gene showed MI (P = 0.018). In addition, we found that MI w as not associated with the prognosis. Our data suggest that MI plays a sign ificant role in non-small cell lung cancer tumorigenesis in Taiwan and that MI is associated with the altered expression of hMLH1 mismatch repair prot ein. In addition, MI may be involved in frequent small intragenic deletions of p53 gene.