Insulin Growth Factor Receptor-1 (IGF-1R) Overexpression Is Associated with Hormone Receptor Positive Ductal Carcinomas in African-American Women
Ashwini K Esnakula, Luisel J Ricks-Santi, Wayne AI Frederick, Yasmine Kanaan, Tammey J Naab. Howard University Hospital, Washington, DC
Background: Insulin-like growth factor receptor 1 (IGF-1R) is a transmembrane tyrosine kinase receptor protein, activated by insulin growth factors (IGF). IGF-1R mediates the growth promoting actions of IGF-1 and IGF-2 by downstream activation of multiple pathways leading to differentiation, proliferation and enhanced survival. The objective of our study is to correlate the immunohistochemical expression of IGF-1R in the four major subtypes of breast carcinoma (luminal A, luminal B, HER2 positive, and Triple Negative) and with clinicopathological factors in African American women.
Design: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast ductal carcinomas in 203 African-American females. Two separate 1mm cores represented each case. Tumors were subtyped based on expression of ER, PR, HER2, vimentin and 34βE12. Immunohistochemical evaluation for IGF-1R was performed using rabbit monoclonal antibody (G11, Ventana, AZ, USA). The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells; and H-score was calculated. Previous studies have reported that normal breast tissue showed moderate expression of IGF1-R, hence cases with H-score <100 are considered reduced expression for IGF-1R and cases with H-score >200 were considered as overexpression for IGF-1R expression. Bivariate analysis was done via χ2 analysis and multivariate analysis was done via Cox's proportional hazards model. Statistical significance was assumed if P < 0.05.
Results: Among our study population, 43.8% were Luminal A, 14.4% Luminal B, 8.5% HER2 positive, and 33.3% triple negative of which 51% were basal-like phenotype. IGF-1R overexpression was significantly linked to ER+ (P<0.0001), PR+ (P=0.0186), HER2- (P=0.0229), and Luminal A breast cancer subtype (P<0.0001). However, 29% of triple negative cases showed high IGF-1R expression. IGF-1R expression was not associated with age, grade, stage or survival. There was trend towards better overall survival in low IGF-1R expressing ER+ tumors when compared to IGF-1R overexpressed ER+ tumors.
Conclusions: Our study found that IGF-1R overexpression was significantly associated with hormone positive breast cancer suggesting that IGF-1R signaling might play a potential role in pathogenesis of ER+ tumors. Monoclonal antibodies targeting IGF-1R are already under clinical investigation in treatment of various solid organ and soft tissue tumors. Targeting IGF-1R in chemotherapy resistant ER+ breast cancer could be beneficial.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 12, Wednesday Afternoon