A Study of Microsatellite Instability in Primary Small Cell Lung Cancer by Microsatellite Analysis

BACKGROUND: Genomic instability, which is manifested by the replication error (RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer ( as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. METHODS: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with both primary tumor and corresponding control tissue were investigated. This phrase is unclear. Does this mean the blocks contained both primary tumor and control tissue samples? Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. RESULTS: 1) Thirteen (86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. 2) Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. 3) LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). 4) Nine (60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. 5) Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5% (mean 9.4% +/-16.19)(Table 2). 6) Shifted bands occurred in 5.7% (34 of 600) of the loci tested Table 2. 7) Nine cases with shifted bands exhibited LOH ranging between 0~83.3%(,) and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%(,) and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). CONCLUSION: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.ope