Prognostic Significance of Fibroblast Growth Factor Receptor 1 (FGFR-1) Overexpression in Invasive Mammary Carcinoma (BRCA)
Michael J Presta, Rami N Al-Rohil, Christopher B Sheehan, Christine E Sheehan, Ann B Boguniewicz, Jeffrey S Ross. Albany Medical College, Albany, NY
Background: FGFR-1 is a multifunctional polypeptide growth factor receptor that has a well established role in angiogenesis and tumorigenesis. Although amplification of the FGFR1 gene has been linked to adverse prognosis in human BRCA, the prognostic significance of FGFR-1 protein expression is not well characterized.
Design: Formalin-fixed, paraffin-embedded tissue sections from 129 cases of BRCA [102 ductal carcinomas (IDC) and 27 lobular carcinomas (ILC)] were immunostained by a manual method using rabbit polyclonal Flg (FGFR-1) (sc 121; Santa Cruz Biotech, Santa Cruz, CA). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: FGFR-1 immunoreactivity was present in a predominately cytoplasmic pattern. Cytoplasmic FGFR-1 overexpression was observed in 85/129 (66%) tumors and correlated overall with advanced stage [79% advanced stage vs 55% early stage, p=0.005], disease recurrence [79% recurrent vs 60% non-recurrent, p=0.03], and survival on Cox univariate analysis (p=0.05). Within the IDC subgroup, FGFR-1 overexpression correlated with advanced stage [81% advanced stage vs 58% early stage, p=0.011]. Within the ER negative subgroup, FGFR-1 overexpression correlated with early age at diagnosis [92% <45 years of age vs 43% diagnosed between 45-55 years of age vs 47% >55 years, p=0.021] and advanced stage [75% advanced stage vs 44% early stage, p=0.037], while showing a trend toward correlation with disease recurrence [74% recurrent vs 46% non-recurrent, p=0.066]. On multivariate analysis, early age at diagnosis (p=0.006) and advanced stage (p<0.0001) independently predicted disease recurrence; and advanced stage (p<0.0001) independently predicted overall survival.
Conclusions: Cytoplasmic FGFR-1 overexpression correlates with advanced stage and disease recurrence in BRCA. In an ER negative subgroup, cytoplasmic overexpression correlates with early age at diagnosis and advanced stage. Expression also shows a trend towards correlation with disease recurrence. On multivariate analysis, diagnosis at an early age and advanced stage independently predicts disease recurrence, and advanced stage independently predicts overall survival. Further study of FGFR-1 expression as a prognostic factor and potential target of therapy for BRCA appears warranted.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 36, Monday Morning