Brief Report: Androgen Receptor Expression Is Associated With Male Predominance in Thymic Neuroendocrine Neoplasms

Abstract

Introduction

Neuroendocrine neoplasms represent a rare and poorly understood collection of malignancies. A better understanding of their biology is needed to improve treatment options. Male predominance to the incidence of neuroendocrine neoplasms of the thymus suggests a biological basis for this observation.

Methods

This single-institution, retrospective cohort study evaluated androgen receptor (AR) expression and other clinicopathologic features in thymic neuroendocrine neoplasms compared with thymic epithelial tumors and neuroendocrine neoplasms of other sites. Expression of neuroendocrine and prostate markers was also assessed. For further molecular characterization, copy number analysis of AR and other relevant genes was assessed by single nucleotide polymorphism array. Last, analysis of single genes and thymic epithelial gene sets was performed using published thymic tumor transcriptomes.

Results

A cohort was assembled from 17 patients with neuroendocrine malignancies of primary thymic origin with assessable tissue for immunohistochemical analysis. The cohort was predominantly male (12 males, five females). Immunohistochemical analysis of the AR demonstrated positive staining in nine cases, all of which were male. Compared with thymic neuroendocrine neoplasms, AR expression is considerably less frequent in thymomas, thymic carcinoma, and neuroendocrine neoplasms of other sites of origin. No relevant copy number changes in the AR were identified. Further molecular characterization revealed expression of ASCL1 and limited expression of common prostate lineage and differentiation markers within our cohort, including thymic neuroendocrine epithelial gene set enrichment in published transcriptomes of thymic neuroendocrine neoplasms.

Conclusion

The AR is expressed in a considerable fraction of thymic neuroendocrine neoplasms and is associated with male predominance. This observation has implications for investigation of androgen deprivation and receptor blockade.