Androgen Receptor Expression Is Usually Maintained in Initial Surgically-Resected Breast Cancer Metastases, but Often Lost in Terminal Metastases Found at Autopsy.
Ashley Cimino-Mathews, Jessica Hicks, Angelo DeMarzo, Ben Ho Park, Pedram Argani. The Johns Hopkins Hospital, Baltimore, MD
Background: The androgen receptor (AR) is expressed in approximately 70% of primary breast carcinomas (PBCs), including those negative for ER and Her2. AR is a promising therapeutic target for breast carcinoma; however, no prior studies have evaluated AR expression in metastatic breast carcinomas (MBCs) in relation to their matched PBCs. Here, we examine AR expression in a cohort of initial surgically-resected metastases, as well as in a separate cohort of end-stage metastases harvested at autopsy, compared to their respective matched PBCs.
Design: Tissue microarrays (TMAs) were constructed from archived paraffin tissue blocks of PBCs and surgically-resected matched MBCs from 16 patients. In addition, we evaluated previously-constructed single patient TMAs constructed from archived paraffin tissue blocks of PBCs and from multiple MBCs sampled at rapid autopsies on 16 patients who died of widely MBC. TMAs were labeled by immunohistochemistry for ER, PR, and Her2 to classify cases into the following categories: luminal (ER/PR+ Her2- in PBC and MBC), triple negative (TNC) (ER/PR/Her2- in PBC and MBC), Her2 (ER/PR- Her2+ in PBC and MBC), and luminal loss (loss of ER or PR from PBC to MBC). AR expression was scored as labeling intensity (none=0, weak=1, moderate=2, strong=3) multiplied by percentage nuclear labeling (0-100%), with any labeling considered a positive result.
Conclusions: AR expression is almost always concordant between matched PBC and surgically-resected MBC, with a trend towards increased expression in MBC. This finding validates AR as a therapeutic target in MBC and suggests that AR expression may need to be reevaluated in MBC even if the PBC is negative. However, AR expression is decreased with a trend towards complete loss in end-stage MBC, particularly in the setting of cases showing hormone receptor loss (luminal loss cases). This suggests a shift of AR expression between initial and end-stage MBC and points to an opportunity for targeted anti-androgen therapy at an earlier stage in disease progression.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 16, Monday Morning