%0 Journal Article
%T Correlation of Oncotype DX Recurrence Score With the Expression of Insulin Receptor Substrate Proteins in Estrogen Receptor + Breast Cancer - Correlation of Oncotype DX Recurrence Score With the Expression of Insulin Receptor Substrate Proteins in Estrogen Receptor + Breast Cancer - Open Access Pub
%A Ashraf Khan
%A Dina Kandil
%A Jennifer L. Clark
%A Kathryn Edmiston
%A Leslie M. Shaw
%A Shaolei Lu
%A Vighnesh Walavalkar
%J OAP | Home | Journal of Cancer Genetics And Biomarkers | Open Access Pub
%D 2017
%X Insulin receptor substrate (IRS) 1 and 2 are downstream signaling proteins that influence breast pathophysiology. IRS-1 promotes carcinoma cell proliferation; whereas IRS-2 regulates cell motility, invasion, and glycolysis. Our lab has shown that distinct cellular localization of IRS-2 also plays a role in carcinoma cell function. Oncotype DX (Genomic Health) (ODX) is a 21-gene expression profile used to classify carcinomas with low, intermediate, and high risk recurrence scores (RS). Our aim is to correlate expression and cellular localization of IRS proteins in breast carcinomas with their ODX RS. 97 breast carcinomas sent for ODX testing from 2006-2009 were collected and grouped according to their RS (low, intermediate or high). Immunohistochemistry for IRS-1/-2 was performed. Specific criteria were used to evaluate IRS staining patterns. Follow-up data, ranging from 3-6 years, was available. Statistical analysis was performed to correlate staining patterns of IRS-1/-2 with the three RS groups. IRS-1 staining, predominantly nuclear, did not significantly correlate with RS (P=.5645). IRS-2 expression patterns did show statistical significance amongst the three RS groups (P=.0371). Tumors with intermediate and low RS were more likely to exhibit punctate and diffuse cytoplasmic expression of IRS-2, and cell membrane expression was uncommon in this group. Expression and cellular localization of IRS proteins play an important role in breast cancer cell biology, and expression patterns for IRS-2 do demonstrate a significant correlation with ODX RS. Further studies are required to elucidate the significance of cellular localization of IRS-1/-2 proteins in breast carcinoma cells and their relationship to ODX scores. DOI10.14302/issn.2572-3030.jcgb-13-369 The insulin receptor substrate (IRS) adaptor proteins (IRS-1 and IRS-2) are expressed relatively ubiquitously in human tissues and in many cancers.1 They act as signaling intermediates, downstream to multiple cytokine and growth factor receptors which are involved in the regulation of breast carcinoma cell function, including the insulin receptor (IR) and insulin-like growth factor receptors (IGF-1R).1,2,3,4,5,6,7,8 IRS-1 and IRS-2 are expressed in normal mammary epithelium, as well as in benign and malignant breast lesions.3 Despite considerable sequence and structural homology, IRS-1 and IRS-2 have been shown to serve divergent functions.2 IRS-1 expression is estrogen-dependent, promotes cellular proliferation but may inhibit disease progression; whereas progesterone-regulated IRS-2 upregulates glycolysis,
%U https://www.openaccesspub.org/jcgb/article/90