Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

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

YC Wang PhD 1, JW Chang MS 2, YC Chen MS 2, YP Lu MS 1, CY Chen MD 3, JT Chen MD 3

1 National Taiwan Normal University, Taipei, Taiwan, 2 Chung Shan Medical College,, 3 Taichung Veterans General Hospital, Taichung, Taiwan,

AIMS: To investigate the association between genetic instability, mismatch repair alteration, and p53 mutation, we examined the association between microsatellite instability (MI) and hMLH1 mismatch repair gene alteration as well as the association between MI and p53 gene mutations. METHODS: The frequency of MI of 8 dinucleotide repeat markers in 68 patients with non-small cell lung cancer was analyzed. The expression of hMLH1 mismatch repair protein was examined by immunohistochemistry in paraffin-embedded tumors from 64 patients. The promoter methylation of hMLH1 gene was examined by the PCR-based methylation assay in 68 patients. The mutation spectrum of the p53 gene was examined by direct sequencing of 64 patients. RESULTS: Twenty-eight patients (41.2 %) evidenced instability in multiple tested microsatellite markers ranging from 3 to 7 and were defined as MI-positive patients. Twenty MI-positive patients (76.9%) had no expression of hMLH1 protein (P = 0.03) and the negative expression of hMLH protein may associate with hypermethylation of hMLH1 promoter. All patients except one containing small intragenic deletion in p53 gene showed MI (P = 0.018). CONCLUSIONS: Our data suggest that MI plays a significant role in NSCLC tumorigenesis in Taiwan and that MI is associated with the altered expression of hMLH1 mismatch repair protein. In addition, MI may be involved in frequent small intragenic deletions of p53 gene.

KEY WORDS: Microsatellite instability, hMLH1 gene, p53 gene, and NSCLC.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.