Immunohistochemical Overexpression of Platelet-Derived Growth Factor Receptor-Beta (PDGFR-β) is Associated With PDGFRB Gene Copy Number Gain in Sarcomatoid Non-Small-Cell Lung Cancer

Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We conducted immunohistochemical and fluorescence in situ hybridization studies of PDGF-B/PDGFR-b on archived surgically resected specimens and showed high PDGFR-b IHC expression and gene copy number gain. Further studies are warranted to determine whether PDGFR-b is a feasible therapeutic target in this population. Introduction: Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-R beta pathway may be dysregulated in sarcomatoid lung cancer. Methods: We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-beta on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival. Results: Sarcomatoid tumors had higher PDGFR-beta IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-beta IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-beta IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005). Conclusion: This is the first study to demonstrate high PDGFR-beta IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-beta is a feasible therapeutic target in this population.