Glucocorticoid Receptor Expression in Breast Carcinoma Molecular Subtypes: An Immunohistochemical Study.
Kamaljeet Singh, Shaolei Lu, Lolie Noble, Rose Tavares, Ronald DeLellis, Murray Resnick, Evgeny Yakirevich. Rhode Island Hospital/Alpert Medical School of Brown University, Providence
Background: Glucocorticoids (GCs) are steroid hormones involved in a variety of physiologic and pathologic processes, such as cellular differentiation, growth, inflammation, and the immune response. GCs mediate their effect by binding to the glucocorticoid receptors (GRs), which are members of the steroid hormone receptor superfamily expressed in a variety of target tissues, including the breast. Our goal was to systematically evaluate GR expression by immunohistochemistry in the various breast cancer molecular subtypes.
Design: On the basis of IHC expression of ER, HER2, CK5/6 and EGFR a total of 246 consecutive grade 3 invasive ductal carcinoms were stratified into 65 luminal (ER+), 70 HER2 positive (HER2+), 100 basal-like, including 18 metaplastic carcinomas (ER-, HER2-, CK5/6 and /or EGFR+), and 11 all 4 markers negative. Tissue microarrays were analyzed for GR expression by IHC with a rabbit polyclonal Ab PA1-511A and scored semiquantitatively based on the extent and intensity on a scale of 0-3+.
Results: Strong nuclear GR expression was present in normal ductal and lobular myoepithelial cells, whereas luminal cells were negative. In the breast carcinoma cases the staining pattern was similar to that in normal breast with predominant nuclear GR localization. GR expression was found in the majority of the metaplastic breast carcinomas (77.8%), in 45.12% of basal-like subgroup, 29.2% of luminal, 24.3% of HER2+, and 18.2% of all marker negative subtypes (P<0.01). There was a strong positive association of GR expression with basal markers cytokeratin 5/6 and EGFR (P<0.001and P<0.05, respectively). Expression of GR was inversely associated with HER2; however, there was no significant correlation of GR with ER or PR. Significantly more frequent GR expression was associated with tumors of low stage (stage 1 and 2), P=0.04.
|Luminal (ER+)||HER2||Basal-Like Non-metaplastic||Basal-like metaplastic||All Negative|
|GR+||19 (29.2%)||17 (24.3%)||37 (45.1%)||14 (77.8%)||2 (18.2%)|
|GR-||46 (70.8%)||53 (75.7%)||45 (54.9%)||4 (22.2%)||9 (81.8%)|