Clinical Importance of Focal Adhesion Kinase (FAK)-Src and Paxillin Expression in Renal Cell Carcinoma.

ABSTRACT

BACKGROUND AND OBJECTIVE: The complex focal adhesion kinase (FAK)/Src and paxillin seem to play a key role in the pathogenesis and progression of cancer. The aim of this study is to evaluate the expression of these proteins in renal cell carcinomas (RCCs), considering the immunoreactive score (IRS), the positivity and the intensity, and to find any association with patients' clinical characteristics, histologic type and other pathological features that imply a possible pathophysiological or prognostic role of FAK/Src and paxillin in RCC. METHODS: Patients with RCC who had undergone partial or radical nephrectomy from January 2009 to September 2010 were eligible for this retrospective cross-sectional study. The immunohistochemical expression of FAK, Src and paxillin proteins in formalin-fixed paraffin-embedded tumour tissue was analysed in association with various clinicopathological features. RESULTS: Out of ninety patients, 58 had clear cell renal carcinoma, 15 had papillary, 11 had chromophobe and six had unclassified RCC. FAK, Src and paxillin were expressed in 55.6%, 32.2% and 18.9% of all cases, respectively. In univariate analysis, FAK positivity and IRS were more likely in patients with papillary and chromophobe histologic type versus clear cell RCC (p<0.005), Src positivity and IRS presented more frequently in stage T3 versus T1 (p<0.005) and paxillin positivity was more likely in patients with stage T3 versus T2 (p=0.021) and grades 3-4 versus grade 2 (p=0.013). Paxillin-IRS was not associated with any clinicopathological features. The same associations were also reproduced in the multifactorial analysis for the FAK and Src positivity and IRS, while it was found that paxillin positivity and IRS were associated with the female gender (p=0.052, p=0.024), and were higher in grades 3-4 versus grade 2 (p=0.022, p=0.020). CONCLUSIONS: Our study suggests that RCC shows immunohistochemical expression of FAK, Src and paxillin proteins, and this expression varies in relation to the histologic type, the stage and the stage/grade/gender, respectively. These findings imply a possible involvement of the FAK/Src signalling pathway in the pathogenesis and progression of cancer in RCC, providing future perspectives for targeted therapies with inhibitors.