Abstract 2877: Focal adhesion kinsase (FAK) protein overexpression and gene copy number gain correlate with better outcome in patients with surgically resected NSCLC tumors

Abstract

Abstract Purpose: Cancer cell migration mechanisms are important for invasion and metastasis development. Focal adhesion kinase (FAK) is a critical cancer-related signaling molecule that regulates cell motility and migration. We investigated the effect of tumor FAK protein expression and gene copy number gain in the prognosis of patients with surgically resected non-small cell lung cancer (NSCLC). Material and Methods: We studied FAK protein expression by immunohistochemistry (IHC) in 216 NSCLC stages I-III archival tumors, including 151 adenocarcinomas (ACs) and 65 squamous cell carcinomas (SCCs). In 190 of these tumors (132 ACs and 58 SCCs), we examined FAK gene copy number by fluorescence in situ hybridization (FISH). FAK IHC expression was examined using the H-score, and a score >150 was defined as overexpression. We examined the correlation of FAK abnormalities with tumors' clinic-pathological and molecular features, and with patients' outcome, including recurrence free and overall survivals. Results: FAK cytoplasmic protein expression score (P<0.0001) was significantly higher in AC (143 ± 71) compared to SCC (70 ± 42) histology, and in never smokers than smokers. FAK protein overexpression was more frequently (P=0.0005) detected in stage I (46%) than stage II (22%) and III (23%) tumors. In ACs, FAK protein overexpression was significantly higher (P=0.003) in tumors with EGFR mutation (11/13, 85%) compared with wild-type tumors (40/97, 41%). We found that ≥4 FAK gene copies in ≥20% of malignant cells were detected in 28.8% of ACs and 22.4% of SCCs. We did not find correlation between protein expression and gene copy number. After adjusting for stage and adjuvant therapy, NSCLC and AC patients with FAK expression higher than the median had better overall survival (NSCLC, HR 0.51 [CI 0.29-0.86], P=0.017; AC, HR 0.43 [CI 0.23-0.82], P=0.011) compared with patients without protein overexpression. Also, we found that, after adjusting for stage and adjuvant therapy, FAK gene copy number ≥4 in ≥20% of tumors cells correlated with better overall survival (HR 0.34 [CI 0.16-0.95], P=0.039) in patients with AC histology. Conclusion: FAK protein overexpression and gene copy number gain were frequently detected in NSCLC tumors, and, interestingly, they correlated with better outcome in patients with surgically resected tumors. Citation Format: Ximing Tang, Yiran Cai, Carmen Behrens, Heather Lin, J. Jack Lee, Ignacio. I. Wistuba. Focal adhesion kinsase (FAK) protein overexpression and gene copy number gain correlate with better outcome in patients with surgically resected NSCLC tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2877. doi:10.1158/1538-7445.AM2014-2877