Fibroblast Growth Factor 2 (FGFR-2) Overexpression Is Associated with High Tumor Grade and Advanced Stage in Prostatic Adenocarcinomas (PACs)
Guilian Niu, Wadad S Mneimneh, Bhaskar VS Kallakury, Gregory M Sheehan, Christine E Sheehan, Hugh AG Fisher, Ronald P Kaufman, Jr., Tipu Nazeer, Jeffrey S Ross. Albany Medical College, Albany, NY; Georgetown University Hospital, Washington, DC
Background: The fibroblast growth factor (FGF) and their receptors (FGFR) have a well established role in angiogenesis and tumorigenesis and have recently emerged as critical mediators of 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 prostatic carcinogenesis, this is the first study on the prognostic significance of Bek/FGFR2 expression in these tumors.
Design: Formalin-fixed, paraffin embedded sections from 136 PACs were immunostained by a manual method rabbit polyclonal FGFR-2 antibody (sc-122; Santa Cruz Biotech, Santa Cruz, CA). Cytoplasmic immunoreactivity was scored based on intensity and percentage of positive cells in the tumor epithelium in each case. Results were correlated with clinicopathologic variables.
Results: Tumor immunoreactivity was predominantly cytoplasmic for the FGFR-2 protein, while occasional nuclear positivity was observed. Intense diffuse cytoplasmic FGFR-2 overexpression found in 46/136 (34%) correlated with high tumor grade (48% high grade vs 24% low grade, p=0.003) and advanced tumor stage [47% advanced stage vs 24% early stage, p=0.006]. FGFR protein was also prominently expressed in the basal epithelial cells of benign prostatic acini. Nuclear expression found in 78/136 (57%) cases correlated with high tumor grade (71% high grade vs 48% low 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.
Conclusions: The increased expression of FGFR-2 in a subset of aggressive prostate carcinomas may offer an attractive target for the recently expanding monoclonal antibody therapeutic applications, worthy of further study.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 148, Monday Morning