Androgen Receptor Expression in Breast Cancer Molecular Classes: An Immunohistochemical Study of 190 Consecutive Cases
LA Niemeier, DJ Dabbs, JM Striebel, R Bhargava. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have growth inhibitory effects on estrogen receptor (ER) and progesterone receptor (PR) negative breast cancer cell lines that demonstrate androgen receptor (AR) expression. These laboratory findings may be translated into inexpensive alternative therapies for ER-/PR- invasive breast cancers (IBCs). Our aim was to systematically evaluate AR expression by immunohistochemistry (IHC) in breast cancer molecular classes.
Design: AR (clone AR441, Dako) expression was analyzed on 190 IBCs represented with 3-fold redundancy on tissue microarrays. The IBCs were classified using IHC surrogate (to molecular classes) markers-ER, PR and HER2. ER and PR were scored using a semi-quantitative H-score method with a dynamic range of 0-300. HER2 was considered positive only if 3+ by IHC or unequivocally amplified by FISH. The tumors were divided in 6 groups as follows: Luminal A (LUMA; ER score 200 or higher, HER2 negative), Luminal B (LUMB; ER score 11-199 or PR >10, HER2 negative), Triple Negative (TN; ER and PR score 10 or less, HER2 negative), ERBB2 (ER and PR score 10 or less, HER2 positive), Luminal A-HER2 Hybrid (LAHH; ER score 200 or higher, HER2 positive), Luminal B-HER2 Hybrid (LBHH; ER score 11-199 or PR >10, HER2 positive). AR expression was also semiquantitated using an H-score method and a score >10 was considered as positive.
Results: Of the 190 consecutive IBCs, 152 (80%) were positive and 38 (20%) were negative for AR. The AR expression with respect to molecular classes was as follows:
|LUMA||103 (96%)||4 (4%)||107|
|LUMB||24 (86%)||4 (14%)||28|
|TN||3 (10%)||27 (90%)||30|
|ERBB2||5 (63%)||3 (37%)||8|
|LAHH||9 (100%)||0 (0%)||9|
|LBHH||8 (100%)||0 (0%)||8|
Of the 8 ER-/PR-/AR+ tumors (5 of ERBB2 and 3 of TN group), 6 demonstrated apocrine differentiation.
Conclusions: Molecular classes LUMA, LUMB, LAHH, LBHH (i.e. ER+ tumors) demonstrate AR expression in the majority of cases. TN tumors show AR expression only in a subset of tumors that demonstrate apocrine differentiation. A vast majority of ERBB2 tumors are AR positive due to overwhelming presence of apocrine differentiation in these tumors. AR targeted therapy in ER-/PR- tumors may provide an inexpensive alternative to usual high dose chemotherapy with or without trastuzumab.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 42, Monday Morning