Document Type: Original Research
Cancer Molecular Pathology Research Center, Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Background & Objective: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was to evaluate the possible relation between FGFR1 over-expression and amplification in TNBCs and other clinicopathological variables.
Methods: In this cross sectional study, purposive sampling was used to collect eighty-four TNBC specimens from mastectomy specimens collected between 2013 and 2017. Tissue microarrays were evaluated for FGFR1 over-expression and amplification respectively by immunohistochemistry (IHC) staining and real time Polymerase Chain Reaction (PCR). The needed clinical and paraclinical information were obtained from patients’ files. To analyze the correlation among prognostic factors, we used a wide range of different statistic methods, namely Chi-square test, independent t-test, Fisher's exact test, and ANOVA.
Results: FGFR1 over-expression was found in 15 of the 84 samples (17.9%). FGFR1 gene amplification was observed in 33.3% (28 of 84) of the samples. We found no association between FGFR1 and clinicopathological parameters, including tumor grade, stage, and patient survival (P>0.005).
Conclusion: FGFR1 over-expression and amplification may not be related to clinicopathological parameters, namely age, stage, and grade of the cancer not to mention TNBC survival. Using FGFR1 as a prognostic factor in TNBCs requires further study.
- Davis SL, Eckhardt SG, Tentler JJ, Diamond JR. Triple-negative breast cancer: bridging the gap from cancer genomics to predictive biomarkers. Therapeutic Adv Med Oncol 2014; 6(3): 88-100. [DOI:10.1177 /1758834013519843] [PMID] [PMCID]
- Chioni AM, Grose R. FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior. J Cell Biol 2012; 197(6): 801-817. [DOI:10.1083/jcb. 201108077] [PMID] [PMCID]
- André F, Cortés J. Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. Breast Cancer Res Treat 2015; 150(1): 1-8. [DOI:10.1007/s10549-015-3301-y] [PMID] [PMCID]
- Dienstmann R, Rodon J, Prat A, et al. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann Oncol 2014; 25(3): 552-563. [DOI:10.1093/annonc/mdt419] [PMID] [PMCID]
- Brown W, Tan L, Smith A, Gray NS, Wendt MK. Covalent targeting of fibroblast growth factor receptor inhibits metastatic breast cancer. Mol Cancer Ther 2016; 15(9): 2096-2106. [DOI:10.1158/1535-7163.MCT-16-0136] [PMID] [PMCID]
- Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metas Rev 2015; 34: 479-496. [DOI:10.1007/s10555-015-9579-8] [PMID] [PMCID]
- Butti R, Das S, Gunasekaran VP, Yadav AS, Kumar D, Kundu GC. Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Mol Cancer 2018; 17: 34. [DOI:10.1186/s12943-018-0797-x] [PMID] [PMCID]
- Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Goto-Yamaguchi L, Fujiki Y, Fujiwara S, et al. Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer. Cancer Sci. 2016; 107(4): 491-8. [DOI:10.1111/cas.12897] [PMID] [PMCID]
- Nicholas Turner, Alex Pearson, Rachel Sharpe, et al. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res 2010; 70(5): 2085-2094 [DOI:10.1158/0008-5472.CAN-09-3746] [PMID] [PMCID]
- Jain VK, Turner NC. Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer. Breast Cancer Res 2012; 14(3): 208. [DOI:10.1186/bcr3139] [PMID] [PMCID]
- Elbauomy Elsheikh S, Green AR, Lambros MB, et al. FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res 2007; 9(2): R23. [DOI:10.1186/bcr1665] [PMID] [PMCID]
- Maryam Ghasemi, Laleh Vahedi Larijani, Omid Emadian, Jamshid Yazdani, Amad Sajadianfar and et al. Immunohistochemical Investigation of Mutant BRAF V600E in Common Pigmented Skin Neoplasms, Study on a Sample of Iranian Patients. Iran J Pathol.2019; 14(1):8-16 [DOI:10.30699/ijp.14.1.8] [PMID] [PMCID]
- Lorenz TC. Polymerase chain reaction: basic protocol plus troubleshooting and optimization strategies. J Vis Exp. 2012;(63):e3998. [DOI:10.3791/3998] [PMID] [PMCID]
- Lee HJ, Seo AN, Park SY, Kim JY, Park JY, Yu JH, et al. Low Prognostic Implication of Fibroblast Growth Factor Family Activation in Triple-negative Breast Cancer Subsets. Ann Surg Oncol 2014; 21(5): 1561-8. [DOI:10.124 5/s10434-013-3456-x] [PMID]
- Nedeljković M, Tanić N, Dramićanin T, Milovanović Z, Šušnjar S, Milinković V, et al. Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer. J Biomed Chem 2018; (37): 1-8. [DOI:10.2478/jomb-2018-0012] [PMID] [PMCID]
- Cheng CL, Thike AA, Tan SY, Chua PJ, Bay BH, Tan PH. Expression of FGFR1 is an independent prognostic factor in triple-negative breast cancer. Breast Cancer Res Treat. 2015; 151(1): 99-111. [DOI:10.1007/s10549-015-3371-x] [PMID]
- Rachel Sharpe, Alex Pearson, Maria T. Herrera-Abreu, Damian A. Johnson and et al. FGFR signalling promotes the growth of triple negative and basal-like breast cancer cell lines both in vitro and in vivo. Clin Cancer Res June 28 2011 [DOI:10.1158/1078-0432.CCR-10-2727] [PMID] [PMCID]
- Lee HJ, Seo AN, Park SY, Kim JY, Park JY and et al. Low prognostic implication of fibroblast growth factor family activation in triple-negative breast cancer subsets. Ann Surg Oncol. 2014 May;21(5):1561-8. [DOI:10.1245/ s10434-013-3456-x] [PMID]