REDUCED SURVIVAL IN PATIENTS WITH STAGE-I NON-SMALL-CELL LUNG-CANCER ASSOCIATED WITH DNA-REPLICATION ERRORS

To better understand whether replication-error-type instability (RER+) is a frequent genetic alteration event in surgical-pathologic stage-1 non-small-cell lung cancer (NSCLC) and identify whether it constitute s an independent prognostic parameter, we examined 35 surgical-patholo gic stage-1-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 microsatelli te markers located at chromosomes 3p and 2p to investigate microsateIl ite alterations such as RER+ and loss of heterozygosity (LOH). Single- strand-conformation-polymorphism analysis for detection of p53 and k-r as gene mutations was also carried out. Genetic data were correlated w ith clinical outcome and histopathologically established prognostic fa ctors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlati on was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased surv ival, ranking first, followed by visceral pleural invasion. A trend to wards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalitie s, such as K-ras mutations, p53 mutations or LOH, had prognoses simila r to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic inf ormation in stage-1 NSCLC and serve as a useful marker for relapse-ris k assessment in operable NSCLC patients. (C) 1997 Wiley-Liss, Inc.