Abstract 2404: Prognostic significance of FGFR-2 immunohistochemical expression in breast and prostate adenocarcinomas.
Authors: Kallakury Bhaskar VS , Sheehan Christine E. , Ross Jeffrey S. 
Published: August 2014

Background: The fibroblast growth factor receptors (FGFR) are tyrosine kinase receptors with a well established role in angiogenesis and tumorigenesis, mediating transformation and progression in animal and human tumors. Their oncogenic role is well documented in human tumors of colonic, renal, urothelial, pancreatic, pulmonary and oral origin. Although a few reports of FGF/FGFR have demonstrated their influence in breast and prostate carcinogenesis, this is the first clinical study demonstrating the prognostic significance of FGFR-2 expression in these tumors.

Design: Formalin-fixed, paraffin-embedded tissue sections from 126 breast [102 ductal carcinomas (IDC) and 24 lobular carcinomas (ILC)] and 136 prostate cancers were immunostained by a manual method using rabbit polyclonal FGFR-2 antibody (sc 122; Santa Cruz Biotech, Santa Cruz, CA). Cytoplasmic and nuclear immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.

Results: In breast, intense diffuse cytoplasmic FGFR-2 overexpression was observed in 35/126 (28%) tumors and correlated overall with tumor type (46% ILC vs 24% IDC, p=0.028), disease recurrence (p=0.031) and shortened survival (p=0.048); within the IDC subgroup, with disease recurrence (p=0.001) and shortened survival (p=0.018); and within the ER negative subgroup, with advanced stage (p=0.027) and disease recurrence (p=0.002). On multivariate analysis, early age at diagnosis (p&lt;0.0001), metastatic disease (p&lt;0.0001) advanced stage (p=0.004), and intense diffuse cytoplasmic FGFR-2 overexpression (p=0.013) independently predicted disease recurrence; while advanced stage (p&lt;0.0001) and metastatic disease (p&lt;0.0001) independently predicted overall survival. In prostate, intense diffuse cytoplasmic FGFR-2 overexpression found in 46/136 (34%) correlated with high tumor grade (p=0.003) and advanced tumor stage (p=0.006). Nuclear expression found in 78/136 (57%) cases correlated with high tumor grade (p=0.005). On multivariate analysis of clinicopathologic parameters and FGFR-2 overexpression, advanced tumor stage (p=0.0002) independently predicted biochemical disease recurrence.

Conclusion: Cytoplasmic overexpression of the FGFR-2 protein is an independent prognostic factor in breast cancer and correlates with poor prognostic variables in prostate cancer. Further study of FGFR-2 expression, including comprehensive genomic profiling to understand the genomic basis of FGFR-2 overexpression, and to further define its potential role as a target of therapy in breast and prostate cancers appears warranted.

Citation Format: Bhaskar VS Kallakury, Christine E. Sheehan, Jeffrey S. Ross. Prognostic significance of FGFR-2 immunohistochemical expression in breast and prostate adenocarcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2404. doi:10.1158/1538-7445.AM2013-2404