The evaluation of Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor 2 (FGF2), Phosphatidyl Inositol 3 Phosphate Kinase (IP3K) expression and their clinical, prognostic significance in early and advanced stage of squamous cell carcinoma of the lung

Aim: Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer related death in the world. Squamous cell carcinoma (SCC) of the lung is the second most frequent histological subtype of lung carcinoma. Recently, growth factors, growth factor reseptors and signal transduction system related gene amplifications and mutations are extensively under investigation to estimate the prognosis or to develope indivilualized therapies in SCC. In this study, besides signal transduction molecule (IP3K p110α), we explored the expressions of growth factors/receptors (FGFR1, FGF2) in tumor tissue and also their clinical or prognostic significance in patients with early/advanced diseases of SCC. Materials and methods: From 2005 to 2013, 129 patients (23 early disease, 106 advanced disease) with a histopathological SCC diagnosis were selected from hospital files of Cukurova University Medical Faculty for this study. In 99 patients with sufficient tissue samples, FGFR1, FGF2 and PI3K (p110α) expressions in both tumor and stromal tissue were evaluated with immunohistochemistry by two independent pathologists. Considering survival analysis seperately for patients with both early and advanced stage diseases, the relationship between the clinical features of patients and expressions were evaluated by univariate and multivariate analysis. Results: FGFR1 expression was found to be low in 59 (60 %) patients and high in 40 (40 %) patients. For FGF2; 12 (12 %) patients had high , 87 (88 %) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, survival was significantly associated with stage and performance status (PS) (p 0.0001 and p 0.001). There was no a significant difference in survival between patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were seperately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (respectively p=0,002, p=0,06 and p=0,05). Discussion: There has not been an effective individualized treatment for SCC, yet. Therefore, for developing such a treatment in future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviours and carcinogenesis of SCC. Although we couldn‟t show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SCC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. However, we layed emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions.