title: Expression of fibroblast growth factor receptor 1, fibroblast growth factor 2, phosphatidyl inositol 3 phosphate kinase and their clinical and prognostic significance in early and advanced stage of squamous cell carcinoma of the lung.
abstract: OBJECTIVE
  Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC.
  
  
  METHODS
  From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses.
  
  
  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, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately 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 (P=0.002; P=0.06 and P=0.05, respectively).
  
  
  CONCLUSIONS
  There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some 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.
authors.affiliation: Department of Medical Oncology, Istanbul Training and Research Hospital Istanbul, Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Usul Afsar
authors.affiliation: Department of Medical Oncology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Berksoy
authors.initials: B
authors.lastname: Sahin
authors.affiliation: Department of Medical Oncology, Bakirkoy Sadi Konuk Research and Treatment Hospital Istanbul, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Gunaldi
authors.affiliation: Department of Pathology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Kılıc Bagir
authors.affiliation: Department of Pathology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Gumurdulu
authors.affiliation: Department of Bioistatistics, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Refik
authors.initials: R
authors.lastname: Burgut
authors.affiliation: Department of Medical Oncology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Melek
authors.initials: M
authors.lastname: Erkisi
authors.affiliation: Department of Medical Oncology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Ismail Oguz
authors.initials: IO
authors.lastname: Kara
authors.affiliation: Department of Medical Oncology, Cukurova University Medical Faculty Adana, Turkey.
authors.forename: Semra
authors.initials: S
authors.lastname: Paydas
authors.affiliation: Department of Radiation Oncology, Adana Numune Research and Education Hospital Adana, Turkey.
authors.forename: Feryal
authors.initials: F
authors.lastname: Karaca
authors.affiliation: Department of Medical Oncology, Mersin State Hospital Mersin, Turkey.
authors.forename: Vehbi
authors.initials: V
authors.lastname: Ercolak
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGF2; FGFR1; IP3K; Squamous cell carcinoma of the lung; prognosis