[300] 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.
Results:

 Staining patternLow RS (n=55)Intermediate RS (n=30)High RS (n=12)p-value
IRS1Nuclear231950.5645
 Negative32117 
      
IRS2Diffuse(D)11550.0371
 Membrane(M)523 
 Punctate(P)37173 
 Negative261 


IRS1 staining did not correlate with RS (p=0.5645). The distribution of D, P, M and negative patterns for IRS2 was significant among the different RS groups (p=0.0371). The D pattern was seen more in the high(41.67%), versus the intermediate(16.67%) and low RS groups(20%). The M pattern was seen more in the high(25%), versus the intermediate(6.67%) and low RS groups(9.09%). The P pattern was seen more in the low(67.27%), versus the intermediate(56.67%) and high RS groups(25%).
Conclusions: The expression and cellular localization of IRS2 protein plays an important role in the biology of breast carcinoma cells. Diffuse and membranous patterns of staining for IRS2 in breast carcinoma cells significantly correlate with high RS, whereas punctate patterns of staining correlate with low RS and may be useful in a clinical setting where Oncotype DX testing is unavailable.
Category: Breast

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 34, Wednesday Morning

 

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