Abstract only 7656 Background: The protein kinase C (PKC) family of serine-threonine protein kinases has been shown to be involved in tumor cell growth, survival, and progression. Tumor-induced angiogenesis requires activation of PKCs, particularly PKCβ, through vascular endothelial growth factor (VEGF) pathways. PKCβ-2 appears to be a major down-stream signaling protein for the VEGFR. This makes PKCβ an attractive target in treatment of malignancies, including lung cancer. Methods: 135 tumor samples (111 Non-small cell lung cancer tissues (52 adenocarcinomas (AC), 34 large cell (LC), 25 squamous cell carcinoma (SCC)) and 24 mesotheliomas (MT)) arranged in tumor microarrays (TMAs) were subject to immunohistochemical staining of PKCβ-1 and PKCβ-2. Results were analyzed manually and scored for intensity (1+, 2+, 3+). Clinical information was available for the AC, LC, and SCC group. Survival curves were generated and median survival between groups was compared utilizing the Log-rank methodology. Results: In NSCLC the expression of PKCβ1 was negative in 1% (1/107), 1+ in 14% (15/107), 2+ in 43% (46/107), 3+ in 42% (45/107); PKCβ2 immunostaining was negative in 28.4% (29/102), 1+ in 12.7% (13/102), 3+ in 23.6% (24/102) and 3+ in 35.3% (36/102). Median survival was superior for patients who expressed PKCβ1 (2+ or 3+) as compared to non-expressors (median survival 1258 days versus 124 days, p<0.001). There was no difference in median survival in patients whose tumors expressed PKCβ2 and those that did not express it. In mesothelioma, staining for PKCβ1 was negative in 0, 1+ in 0, 2+ in 8.3% (2/24) and 3+ in 91.7% (22/24). For PKCβ2, tissues stained negative in 56.5% (13/23), 1+ in 21.8% (5/23), 2+ in 8.7% (2/23), 3+ in 13% (3/23). Median survival was superior for patients whose tumors did not express PKC-beta 2 (0 or 1+) as compared to expressors (median survival 604 days versus 103 days, p<0.001). Conclusions: PKCβ is expressed in NSCLC and mesothelioma. PKCβ1 expression is a favorable prognostic factor in NSCLC, whereas expression of PKCβ2 is an adverse prognostic factor in mesothelioma. Therapeutic targeting of this molecule would be useful for the future. No significant financial relationships to disclose.