A Study of Smoking, p53 Tumor Suppressor Gene Alterations and Non-Small Cell Lung Cancer

Abstract PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53 IHCS ) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53 IHCS > 1. p53 IHC was associated with increasing tumor size (T) ( p = 0.035), nodal status (N) ( p = 0.091), stage ( p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) ( p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34–14.90]. p53 IHC was not associated with smoking variables. In multivariate proportional hazards analysis, p53 IHCS and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53 IHCS and PY were 1.20 (95% CI 1.02–1.40) and 1.03 (95% CI 1.01–1.04), and for death due to recurrent disease ( DRD ) were 1.35 (95% CI 1.11–1.64) and 1.03 (95% CI 1.01–1.04), respectively. Comparing the 75 th percentile to the baseline 0, the adjusted HR for p53 IHCS (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for the outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53 IHCS are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC.