Correlation of Oncotype DX Recurrence Score with IRS1 and IRS2 Protein Expression and Cellular Localization in Breast Cancer
Vighnesh Walavalkar, Dina Kandil, Shaolei Lu, Kathryn Edmiston, Leslie Shaw, Ashraf Khan. UMass Memorial Medical Center, Worcester, MA; Rhode Island Hospital, Providence, RI
Background: Insulin receptor substrate 1 and 2 proteins (IRS1, IRS2) are signaling proteins that impact breast cancer cell function. IRS1 promotes cell proliferation and IRS2 regulates cell motility, invasion and glycolysis. Our previous study has shown a significant correlation between cellular localization of IRS2 and biologic behavior in breast cancer (Breast Cancer Res Treat 2011 Dec;130(3):759-72). Oncotype DX (Genomic Health, Redwood City, CA) is a 21 gene test used to stratify breast cancers with low, intermediate and high risk recurrence scores (RS) which predicts response to chemotherapy. In this study our aim is to correlate IRS1 and IRS2 expression and localization in breast carcinoma cells with their Oncotype DX RS.
Design: 97 breast carcinomas sent for Oncotype DX testing from 2006-2009 were collected from our files and IHC for IRS1 and IRS2 was performed on them. Follow-up data was acquired from our tumor registry. For IRS1 a nuclear staining pattern was defined as diffuse nuclear staining without cytoplasmic staining. IRS2 staining patterns were defined as; Diffuse (D):even cytoplasmic staining without demarcation of cell borders, Punctate (P):distinct cytoplasmic puncta with or without background staining of the cytoplasm, Membrane (M):clear staining of cell borders with or without background staining of the cytoplasm. Statistical correlation for IRS1 and IRS2 with RS was performed.
|Staining pattern||Low RS (n=55)||Intermediate RS (n=30)||High RS (n=12)||p-value|