LOSS OF 18Q PREDICTS POOR SURVIVAL OF PATIENTS WITH SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Tumor suppressor genes play an important role in normal growth regulat ion. Loss or inactivation of these genes has been implicated in the de velopment of squamous cell cancer and progression of neoplasia. Previo us studies in our laboratories have implicated chromosome 18 long-arm deletions as a possible marker of progression in head and neck squamou s cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and fo r association of LOH with survival. Tumor and normal DNA were extracte d from fresh tissue and paraffin blocks and were amplified by PCR usin g primers for three microsatellite repeat polymorphisms in 18q (D18S33 6, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two-year survi val compared to those without 18q LOH (30% vs. 63%; P = 0.008). In a C ox proportional hazards model in which time from diagnosis to death wa s the outcome variable, patients with 18q LOH had an unadjusted relati ve risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study , the RR for death was still elevated (RR = 2.10; P = 0.025), The obse rvation of a prognostic association between 18q LOH and poor patient s urvival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. (C) 1998 Wiley-Liss, Inc.