Background and purpose:Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are receptor tyrosine kinases (RTK) that regulate and control cellular proliferation, differentiation and survival. BAD is the proapoptotic member of the Bcl-2 family that plays an important role in the control of apoptosis especially in tumor cells. However, little is known about the expression of these important proteins in non-small cell lung cancer (NSCLC) in relation to tumor pathology.We studied the expression of EGFR, VEGFR, BAD and phospho-BAD in NSCLC cases and correlated with tumor pathology.Methods:Immunohistochemistry of tissue microarray (TMA) sections was used to study the expression of EGFR, VEGFR, BAD and phospho-BAD in a series of 51 NSCLC cases (26 adenocarcinomas, 16 squamous cell carcinomas, 8 large cell carcinomas and 1 large cell neuroendocrine carcinoma).Results:Overexpression of EGFR and VEGFR was observed in 10 of 51 (20%) and 14 of 51 (27%) cases, respectively. Large cell carcinomas did not demonstrate VEGFR expression (0/8 cases) in contrast to squamous cell carcinoma and adenocarcinoma in which VEGFR expression was observed in 7 of 16 (44%) and 7 of 26 (27%) cases, respectively. EGFR and VEGFR expression was not statistically correlated with gender, tumor cell differentiation, or pathological aggressiveness (measured by pleural invasion, vascular invasion, lymph node metastatic status, intrapulmonary and brain metastasis). Loss of BAD protein expression was observed in 22 of 51 (43%) cases with significant differences among the subtypes of NSCLC. Loss of BAD protein expression was identified in 10 of 16 (63%) squamous cell carcinomas, 5 of 8 (63%) large cell carcinomas and 7 of 26 (27%) adenocarcinomas, with a P value of 0.04. Overexpression of phospho-BAD was observed in 25 of 51 (49%) cases; 13 of 26 (50%) adenocarcinomas, 8 of 16 (50%) squamous cell carcinomas and 4 of 8 (50%) of large cell carcinomas. Loss of BAD protein expression and overexpression of phospho-BAD was not statistically correlated with pathological aggressiveness by the measures mentioned above.Conclusions:Squamous cell carcinoma of the lung is more likely, and large cell carcinoma is least likely to demonstrate increased VEGFR protein expression. Significant loss of BAD protein expression was observed in squamous cell carcinoma and large cell carcinoma. Overexpression of EGFR, VEGFR, phospho-BAD, and loss of BAD expression, did not demonstrate significant correlation with pathological aggressiveness of NSCLC. However, expression of these receptor tyrosine kinases and the mediators directly involved in apoptosis in NSCLC could be used as potential targets for developing a multi targets-oriented therapy in the future.