AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors

• Main Authors: Nelson Rangel, Milena Rondon-Lagos, Laura Annaratone, Andrés Felipe Aristizábal-Pachon, Paola Cassoni, Anna Sapino, Isabella Castellano
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Cells
• Subjects: breast cancer; androgen receptor; estrogen receptor; crosstalk of nuclear receptors; proliferation genes
• Online Access: https://www.mdpi.com/2073-4409/9/4/1064

The co-expression of androgen (AR) and estrogen (ER) receptors, in terms of higher AR/ER ratio, has been recently associated with poor outcome in ER-positive (ER+) breast cancer (BC) patients. The aim of this study was to analyze if the biological aggressiveness, underlined in ER+ BC tumors with higher AR/ER ratio, could be due to higher expression of genes related to cell proliferation. On a cohort of 47 ER+ BC patients, the AR/ER ratio was assessed by immunohistochemistry and by mRNA analysis. The expression level of five gene proliferation markers was defined through TaqMan^®-qPCR assays. Results were validated using 979 BC cases obtained from gene expression public databases. ER+ BC tumors with ratios of AR/ER ≥ 2 have higher expression levels of cellular proliferation genes than tumors with ratios of AR/ER < 2, in both the 47 ER+ BC patients (<i>P</i> < 0.001) and in the validation cohort (<i>P</i> = 0.005). Moreover, BC cases with ratios of AR/ER ≥ 2 of the validation cohort were mainly assigned to luminal B and HER2-enriched molecular subtypes, typically characterized by higher proliferation and poorer prognosis. These data suggest that joint routine evaluation of AR and ER expression may identify a unique subset of tumors, which show higher levels of cellular proliferation and therefore a more aggressive behavior.