Prognostic Significance of Fibroblast Growth Factor Receptor 3 (FGFR-3) Overexpression in Invasive Mammary Carcinoma (BRCA)
Rami N Al-Rohil, Michael J Presta, Bhaskar VS Kallakury, Gregory M Sheehan, Christine E Sheehan, Ann B Boguniewicz, Jeffrey S Ross. Albany Medical College, Albany, NY; Georgetown University Hospital, Washington, DC
Background: The fibroblast growth factor receptor (FGFR) family includes at least 4 tyrosine kinase receptors which have been linked to the development and progression of a variety of human cancers including head and neck squamous cell carcinoma, hepatocellular carcinoma, urothelial carcinoma and multiple myeloma. FGFR-3 expression has not been widely studied as a prognostic factor for BRCA.
Design: Formalin-fixed, paraffin-embedded tissue sections from 126 cases of BRCA [101 ductal carcinomas (IDC) and 25 lobular carcinomas (ILC)] were immunostained by a manual method using rabbit polyclonal FGFR-3 (sc 123; Santa Cruz Biotech, Santa Cruz, CA). Nuclear and cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Intense diffuse cytoplasmic FGFR-3 overexpression was observed in 26/126 (21%) tumors and correlated overall and within the ER- subgroup, with PR+ status (p=0.013, p=0.026) with a trend toward PR+ status within both the IDC (p=0.084) and ILC (p=0.067) subgroups; and overall with disease recurrence (p=0.05), while showing a trend toward disease recurrence within the ER+ subgroup (p=0.06). Nuclear FGFR-3 overexpression was present in 30/126 (24%) tumors and correlated overall and within the IDC subgroup, with ER+ status (p=0.041, p=0.05) and non-recurrent disease (p=0.004, p=0.003). Within the ER+ subgroup, nuclear FGFR-3 overexpression correlated with non-recurrent disease (p=0.017). On multivariate analysis, early age at diagnosis (p<0.0001), advanced stage (p=0.004), lack of nuclear FGFR-3 overexpression (p=0.015), and intense diffuse cytoplasmic FGFR-3 overexpression (p=0.026) independently predicted disease recurrence; while metastatic disease (p<0.0001) and positive node status (p=0.001) independently predicted overall survival.
Conclusions: In summary, loss of nuclear expression and intense cytoplasmic FGFR-3 expression correlate with hormone receptor status and are independent prognostic indicators in BRCA. Further study of FGFR-3 as a prognostic factor and potential target of therapy in BRCA appears warranted.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 33, Tuesday Morning