SRC family kinases are commonly dysregulated in cancer and may thus be therapeutic targets. FYN, a 59 kDa family member, can interact with FAK, paxillin and the MAPK cascade. Upon datamining with Oncomine database (http://www.oncomine.org), FYN expression was upregulated in primary prostate tumors as compared to normal tissue in 7 of 7 studies from human patient samples (give stats). Using human tissue samples in a tissue microarray composed of 0.5 mm sections, we evaluated expression (through IHC) for FYN as well as its signaling partners FAK and paxillin (PXN). Samples on the array were considered adequately represented and thus appropriate for analysis if there were at least 2 samples from a given patient present on the array. After eliminating unusable samples, our analysis included 32 cases of primary prostate cancers (Gleason 6-9), 8 prostatic intraepithelial neoplasia (PIN), and 19 normal prostates. Samples were semi-quantitatively scored for the percentage of positive cells at 10-point intervals and intensity of staining as 0, 1, 2 and 3 for negative, weak, moderate and strong intensity, respectively. Each sample was assigned a composite score generated by multiplying the averages of percentage and intensity of staining. Comparing normal epithelium to cancer, there was a 2.1-fold increase in median composite score for FYN (p<0.001) 1.5-fold increase in FAK (p<0.001), and a 2-fold increase in PXN (p<0.05). There was a 1.4-fold increase in FYN (p<0.001), a 1.6-fold increase in FAK (p<0.001) in cancer tissues as compared to PIN. These studies support the hypothesis that the FYN and its related signaling partners are upregulated in prostate cancer and supports further investigation into the potential role of the FYN as a therapeutic target.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA