Androgen receptor (AR) and phospho-AR protein levels in invasive breast cancers and survival outcomes: Indication of a new prognostic marker.

Abstract

11 Background: Androgen receptor (AR) in breast cancer may serve as a useful prognostic and predictive marker. We examined the expression patterns of AR and AR phosphorylated at serine-213/210 (pAR213/210) in breast cancer by immunohistochemistry, and evaluated their association with clinicopathological parameters and prognoses. Methods: The levels of AR nuclear protein expression were determined in tissue samples of 379 consecutive female patients with invasive breast cancer. In samples that showed detectable AR, the levels of pAR213/210nuclear and cytoplasmic expression were determined. All samples were scored semiquantitatively using a histoscore. Results: Nuclear staining of AR was observed in 76% of the samples. Elevated AR protein expression correlated with non-aggressive parameters and longer relapse-free survival (RFS) (p < .0001) and breast cancer-specific survival (BCSS) (p < .0001). Nuclear and cytoplasmic pAR213/210 were observed in 72.4% and 11.9%, respectively, of the tested samples. Although no statistically significant relationship between pAR213/210 nuclear expression and clinicopathological parameters was observed, increased expression of cytoplasmic pAR213/210 was associated with high nuclear grade (p = .026), estrogen receptor (ER) α-negative (p = .023), progesterone receptor (PgR)-negative (p = .034), human epidermal growth factor receptor 2 (HER2)-positive (p = .043), and Ki-67-positive (p = .026) tumors. Conversely, nuclear pAR213/210 expression correlated with longer RFS (p = .027) and BCSS (p = .0031), but cytoplasmic pAR213/210expression was not related with RFS and BCSS. Conclusions: AR and its phosphorylation at serine-213/210 are significant in breast cancer progression and prognosis. The expression levels of pAR213/210 could have potential as a new prognostic marker of breast cancer.