Clinicopathologic significance of SOX2 and FGFR2 expression in non-small cell lung cancer

Abstract

Introduction: SOX2, a transcription factor for maintenance and pluripotency of embryonic stem cells during development, is overexpressed in lung cancer. Recently, several study reported that SOX2 expression was associated with FGFR2 expression. This study evaluated SOX2 expression in nonsmall cell lung carcinoma (NSCLC) and correlated with FGFR2 gene and protein expression. Methods: Archived NSCLC tissue (training set, n = 389

validation set, n=408) using tissue microarray were analyzed for SOX2 and FGFR2 immunohistochemistry and FGFR2 FISH. The results of immunostaing and FISH were compared each other and correlated with clinicopathologic features of the patients. Results: SOX2 expression was present only in squamous cell carcinoma (p =0.000). SOX2 expression in squamous cell carcinoma was not correlated with FGFR2 expression. FGFR2 protein expression was significantly higher in adenocarcinoma than squamous cell carcinoma (p =0.000). FGFR2 cytoplasmic expression was associated with absence of lymph node metastasis (p =0.016) and lower TNM stage (p = 0.010) in adenocarcinoma of validation set. FGFR2 protein expression was an independent good prognostic factor in adenocarcinoma (p =0.012) of validation set. In squamous cell carcinoma, FGFR2 high gene copy number was identified in 2.7% and 6% tumors of the training and validation set. In adenocarcinoma, FGFR2 high gene copy number was identified in 3.0% and 4.3% of the training and validation set. FGFR2 high gene copy number showed male preponderance. In only training set, FGFR2 gene copy number gain acted as an independent poor prognostic factor in squamous cell carcinoma subgroup (p = 0.003). FGFR2 protein expression and FGFR2 gene copy number gain were not correlated each other in NSCLC. In 8 selected NSCLCs, intratumoral heterogeneity of FGFR2 immunohistochemistry and FGFR2 FISH pattern was observed. Conclusions: SOX2 expression is not exactly correlated with FGFR2 expression in this study. FGFR2 showed various protein expression pattern according to subtype of lung cancer. Increased gene copy number of FGFR2 could be a poor prognostic factor in pulmonary squamous cell carcinoma patients. Discrepancy between FGFR2 protein and gene expression was observed resulting from intratumoral heterogeneity. Further study on expression of FGFR2 isotype and meticulous review of FGFR2 gene state should be proceeded.