Association of Copy Number Loss of CDKN2B and PTCH1 With Poor Overall Survival in Patients With Pulmonary Squamous Cell Carcinoma

Background and Purpose: Although lung cancer is the leading cause of cancer deaths worldwide, reliable markers allowing prediction of patient survival at the time of initial diagnosis are still lacking. Copy number alterations (CNAs) in tumor tissue DNA have been associated with tumorigenesis and malignant progression. We aimed at identification of gene-level CNAs with prognostic value for survival in pulmonary squamous cell carcinoma (SCC). Methods: The CNA status of a panel of 44 genes was analyzed by high-resolution array comparative genomic hybridization (CGH) in 49 SCC samples. Overall survival information (median follow-up, 40 months) for the patients was collected and used to assess outcome correlations with gene CNAs. Results: Survival analysis showed that both CDKN2B loss and PTCH1 loss were associated with poor survival (both P < .001, log-rank test). Multivariate Cox analysis, including CDKN2B loss and PTCH1 loss as well as age, sex, cigarette smoking status, tumor size, tumor differentiation, and TNM stage showed that CDKN2B loss (hazard ratio [HR], 17.88; 95% confidence interval [CI], 4.40-72.67; P < .001) and PTCH1 loss (HR, 10.81; 95% CI, 1.92-60.98; P = .007) were independent prognostic factors for poor survival. In addition the PTCH1 loss was more frequently found in moderately or poorly differentiated tumors than in well-differentiated tumors (P = .007). Conclusion: These findings suggest that 2 genes of loss, CDKN2B and PTCH1, are associated with poor overall survival in patients with SCC of the lung and may be useful as prognostic markers.