Prognostic Significance of Fibroblast Growth Factor Receptor 2 (FGFR-2) Overexpression in Invasive Mammary Carcinoma (BRCA)
Bhaskar VS Kallakury, Rami N Al-Rohil, Michael J Presta, Gregory M Sheehan, Christine E Sheehan, Ann B Boguniewicz, Jeffrey S Ross. Georgetown University Hospital, Washington, DC; Albany Medical College, Albany, NY
Background: FGFRs are tyrosine kinase receptors implicated in carcinogenesis and tumor progression. FGFR-2 expression has been associated with distant metastasis and poor prognosis in colorectal cancer and shortened survival in pancreatic cancer. Although there is substantial evidence linking aberrant FGFR expression in breast cancer, this is the first report to demonstrate prognostic significance of increased FGFR-2 expression in BRCA clinical specimens.
Design: Formalin-fixed, paraffin-embedded tissue sections from 126 cases of BRCA [102 ductal carcinomas (IDC) and 24 lobular carcinomas (ILC)] were immunostained by a manual method using rabbit polyclonal Bek (FGFR-2) (sc 122; 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-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), with a trend toward shortened survival (p=0.06). Nuclear FGFR-2 overexpression was present in 55/126 (44%) and correlated overall and within the IDC subgroup with ER+ status (p=0.05, p=0.05), HER2- status (p=0.042, p=0.05), with a trend toward non-recurrent disease (p=0.069, p=0.067) and early stage (p=0.085, p=0.08); within the ILC subgroup, with tumor size >3.0cm (p=0.034) and PR- status (p=0.035); within the ER+ subgroup, with HER2- status (p=0.021) and lengthened survival (p=0.043). On multivariate analysis, early age at diagnosis (p<0.0001), metastatic disease (p<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<0.0001) and metastatic disease (p<0.0001) independently predicted overall survival.
Conclusions: Cytoplasmic overexpression of the FGFR-2 protein is an independent prognostic factor in BRCA and correlates with both hormonal receptor and HER2 status. Further study of the prognostic significance and potential role as a target of therapy for FGFR-2 in BRCA appears warranted.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 32, Tuesday Morning