[1589] Expression of Focal Adhesion Kinase (FAK), Phosphorylated Focal Adhesion Kinase (pFAK) and Paxillin in Malignant Pleural Mesothelioma (MPM)

S Charoenthammaraksa, M Tretiakova, L Faoro, S Loganathan, R Salgia, T Krausz, AN Husain. University of Chicago, Chicago

Background: FAK and paxillin, focal adhesion proteins, function as positive regulators of cell adhesion and migration via integrin regulated signaling system. We have recently shown paxillin mutations and amplification in lung cancer. Overexpression of these proteins causes cell detachment and migration which is essential for tumor invasion and metastasis. This overexpression correlates with poor clinical outcome as has been reported in many metastatic carcinomas. The expression of FAK, pFAK and paxillin in MPM has not been previously investigated. The aim of our study is to analyze expression of these focal adhesion kinases in MPM compared to normal adjacent lung.
Design: With IRB approval, we used 2 tissue microarray (TMA) blocks containing a 1 mm in diameter tissue cores of MPM (50 epithelioid, 16 sarcomatoid, 1 mixed) and 40 normal adjacent lung parenchyma (pneumocytes and endothelial cells). The TMAs were sectioned and stained by IHC for FAK, pFAK and paxillin. Quantitative staining intensity was analyzed using automated cellular imaging system (ACIS) by calculating average intensity in 500 cells as an integrated optical density (IOD), which is directly proportional to antigen content in cytoplasmic compartment. Fisher's exact test and Pearson correlation were used for statistical analysis in SPSS software, v15.0.
Results:

Histology	Number	FAK_IOD	pFAK_IOD	pFAK ratio	Paxillin_IOD
MPM, Epithelioid	50	273.85	14.65	0.053	268.47
MPM, Mixed	1	231.4	8.07	0.0348	139.39
MPM, Sarcomatoid	16	218.78	12.61	0.057	331.17
Normal Lung	40	45.17	13.54	0.299	118.95

There was a significant increase in FAK and paxillin expression in MPM compared to normal adjacent lung (p<0.01). No significant difference in expression levels of FAK and paxillin between epithelioid and sarcomatoid MPM subtypes was found. High positive correlation between pFAK and paxillin at the 0.01 level (2-tailed) was observed.
Conclusions: Upregulation of FAK and paxillin was present in the majority of MPM of both epithelioid and sarcomatoid types suggesting that these molecules may be good candidates for targeted therapy. Furthermore, we found statistically significant correlation between paxillin and pFAK expression levels. These findings may indicate importance of pFAK and paxillin overexpression in MPM progression, and require further studies in a larger pool of patients to correlate with survival.
Category: Pulmonary

Tuesday, March 10, 2009 11:45 AM

Platform Session: Section F 2, Tuesday Morning