Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors

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Abstract
To better understand whether replication‐error‐type instability (RER+) is a frequent genetic alteration event in surgical‐pathologic stage‐I non‐small‐cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical‐pathologic stage‐I‐NSCLC patients with complete follow‐up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER+ and loss of heterozygosity (LOH). Single‐strand‐conformation‐polymorphism analysis for detection of p53 and k‐ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K‐ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic information in stage‐I NSCLC and serve as a useful marker for relapse‐risk assessment in operable NSCLC patients. Int. J. Cancer 74:330‐334, 1997.