IGF-1R Expression in Normal Breast Tissue, Benign, Proliferative, In-Situ Breast Lesions, and Invasive Breast Carcinoma.
Authors: R. Bhargava, S. Beriwal, D. Dabbs
Journal: Cancer Research (2009)

Abstract There is dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system.IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 invasive breast carcinomas (IBCs) represented with 3-fold redundancy on tissue microarrays. The IBCs were classified using immunohistochemical (IHC) surrogate (to molecular classes) markers-estrogen receptors (ER), progesterone receptors (PR) and HER2. ER and PR were scored using a semi-quantitative H-score like scoring method with a dynamic range of 0-300. An H-score of &amp;gt;10 was considered as positive result and an H-score of 200 or higher was considered as strongly positive. HER2 was considered positive only if 3+ by IHC or amplified (HER2 to chromosome 17 ratio of &amp;gt;2.2) by FISH. The tumors were divided in 6 groups as follows: luminal A (LUMA; strong ER+, any PR, HER2 negative); luminal B (LUMB; weak/moderate ER+ or PR+, HER2 negative); triple negative (TN; ER and PR negative, HER2 negative); ERBB2 (ER and PR negative, HER2+); luminal A-HER2 hybrid (LAHH; strong ER+, any PR, HER2+); luminal B-HER2 positive (LBHH; weak/moderate ER+ or PR+, HER2+). IGF-1R expression was also semi-quantified using an H-score like method but with a dynamic range of 0-400.IGF-1R is expressed at moderate level in normal breast tissue (mean score of 197, median of 200 and stdev of 8). Therefore, normal expression (NE) was defined as IGF-1R IHC scores between 150 and 250, with low expression (LE) below 150 and overexpression (OE) greater than 250. IGF-1R expression in benign, proliferative and in-situ lesions is shown in table 1 and expression level in IBCs is shown in table 2. IGF-1R expression levels among different molecular classes were statistically assessed using chi-square test (SPSS software version 16.0). IGF-1R is differentially expressed in breast cancer molecular classes as determined by IHC (p value &amp;lt;0.0001).Table 1 Mean ScoreMedian ScoreStd DeviationNormal Breast (n=21)1972008Pseudoangiomatous stromal hyperplasia (n=1)00NAApocrine metaplasia (n=9)261026Sclerosing adenosis (n=4)12814056Fibrocystic changes (n=4)1951956Fibroadenoma (n=10)18119534Papilloma (n=3)20021026Ductal hyperplasia (n=3)22322025Columnar cell changes (n=7)23122035Atypical lobular hyperplasia (n=3)21825064Atypical ductal hyperplasia (n=2)24024042Ductal carcinoma in situ (n=4)26526531NA: Not ApplicableTable 2 Low expressionNormal expressionOverexpressionTotalLUMA28 (27%)64 (60%)14 (13%)106LUMB4 (14%)18 (64%)6 (22%)28TN23 (74%)7 (23%)1 (3%)31ERBB28 (100%)0 (0%)0 (0%)8LAHH2 (20%)7 (70%)1 (10%)10LBHH3 (37%)4 (50%)1 (13%)8Total6810023191 IGF-1R OE is seen predominantly in a subset of ER+ tumors. The TN and ERBB2 (HER2+/ER-) tumors essentially do not show IGF-1R OE, and the expression is rather diminished. Our data supports increasing body of evidence that estrogen induces the expression of several members of IGF family. Therefore, determination of IGF-1R expression for therapeutic gains is important only in ER+ tumors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3051.