Background: The oncogenic role of the fibroblast growth factor receptor (FGFR) has been recognized in a number of different cancer types. However, the prognostic significance of FGFRs has not been elucidated yet in cervical cancer. In the present study, we investigate the expression of FGFRs and their prognostic value in cervical cancer patients. Methods: FGFR1, FGFR2, FGFR3, and FGFR4 expression was determined by immunohistochemistry in conjunction with quantitative digital image analysis of 336 formalin-fixed, paraffin-embedded cervical cancer tissues and 61 normal cervical tissues, as well as NCI60 cell microarray. Subsequently, the association between clinicopathological characteristics and patient survival was assessed. Results: FGFRs proteins were differentially expressed in the NCI60 cell line panel and showed considerable correlation between protein and mRNA expression. The expression of FGFR1, FGFR2, and FGFR4 were higher in cancer tissues than in normal tissues, whereas the expression of FGFR3 was higher in normal tissues. FGFR1 was highly expressed in adeno-/adenosquamous carcinoma (P = 0.020), while FGFR2, FGFR3, and FGFR4 expression were more prominent in squamous cell carcinoma (P < 0.001, P < 0.001, and P = 0.020, respectively). FGFR2 expression was significantly higher in small sized tumors (P = 0.020). Additionally, high FGFR2 and FGFR4 were correlated with negative lymph node metastasis (P = 0.048 and P = 0.040, respectively). FGFR1, FGFR2, and FGFR3 were highly expressed in tumors without parametrial involvement (P = 0.030, P = 0.005, and P = 0.010, respectively). In survival analysis, high expressions of FGFR2, FGFR3, and FGFR4 was associated with longer disease-free survival (P = 0.006, P = 0.035, P = 0.001, respectively) and overall survival (P = 0.003, P = 0.002, P = 0.003, respectively). Notably, the co-expression of all three FGFRs was significantly associated with favorable disease-free survival (P < 0.001) and overall survival (P < 0.001), compared to the negative expressions of the three FGFRs. The prognostic significance persisted in the cox regression analysis. Conclusions: The frequent expression of members of the FGFR family in cervical cancer suggests they may have prognostic and therapeutic relevance.
Bibliographical noteFunding Information:
In the present study, we retrieved a total of 336 early stage cervical cancer patients treated in the Department of Gynecologic Oncology, Samsung Medical Center, Sung-kyunkwan University School of Medicine between 2002 and 2009. Patients with rare histology such as sarcoma, malignant melanoma, and neuroendocrine carcinoma, and patients with limited availability of tissue block specimens were excluded from the tissue microarray (TMA) construction. 61 non-matched, non-adjacent normal epithelial tissues were used for the control. Tissue samples were collected from patients who had signed an informed consent form, which was approved by the Institutional Review Board at the Samsung Medical Center, Seoul, Korea (2009-09-002-002 and 2015-07-122). Some of the paraffin blocks were provided by the Korea Gynecologic Cancer Bank through Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF-2012M3A9B8021800). This study was additionally approved by the Office of Human Subjects Research at the National Institute of Health.
This study was supported in part by a Grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Republic of Korea (2013R1A1A2013629) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
© 2016 Choi et al.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)