Hormone receptor (AR/ER/PR) expression as a prognostic marker and novel candidate for drug development across multiple tumor types.

Abstract

2537 Background: Hormone receptor (HR) [androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR)] expression is ubiquitous across tumor types and central to breast and prostate cancer treatment. While implicated in tumorigenesis, its role as a prognostic biomarker and therapeutic target in other tumor types has yet to be elucidated. Methods: We performed bioinformatic analyses of HR expression [reported as median transcripts per million (TPM)] using RNAseq from the Cancer Genome Atlas and completed Kaplan-Meier analyses to identify associations between HR expression and median overall survival (OS). Results: 9,743 samples from 9,674 patients across 33 tumor types were analyzed. AR was highly expressed in GBM (2 TPM), low grade glioma (2 TPM), breast (15 TPM), prostate (14 TPM), ovarian (6 TPM), renal clear cell carcinoma (4 TPM) and HCC (2 TPM) . Tumors with the highest quartile of expression had improved OS in renal clear cell [53 months (mo) vs not reached (NR), p = 4x10-11] and adrenocortical carcinoma (45 mo vs NR, p = .03) and worse OS in low grade glioma (119 vs 64 mo, p = 6x10-4). PR was highly expressed in uterine (12 TPM), breast (5 TPM), and renal chromophobe (2 TPM) carcinoma. PR expression was associated with improved OS in sarcoma (49 mo vs NR, p = .03), endometrial (NR, p = .02) and renal clear cell carcinoma (58 mo vs NR, p = .003) and worse OS in low grade glioma (53 vs 97 mo, p = .01), gastric adenocarcinoma (7 vs 17 mo, p = .04), and possibly pancreatic adenocarcinoma (21 vs 44 mo, p = .07). ER was highly expressed in breast (116 TPM), endometrial (87 TPM), ovarian (32 TPM), cervical (4 TPM), thyroid (4 TPM), prostate (3 TPM), and lung adenocarcinoma (2 TPM). ER expression was associated with improved OS in mesothelioma (15 vs 28 mo, p = .03) and endometrial cancer (NR, p = .001) and worse OS in squamous lung cancer (80 vs 48 mo, p = .02). Conclusions: HR expression may represent a novel prognostic marker in multiple tumor types and a candidate for drug development in low grade glioma, gastric adenocarcinomas, squamous cell lung cancer, and pancreatic adenocarcinomas. Protein-based IHC testing and early phase clinical trials targeting HR signaling in these tumor types is warranted.