Frequent Amplification and Overexpression of PSMA in Basallike Breast Cancer from Analysis of The Cancer Genome Atlas.

Abstract

Prostate-specific membrane antigen (PSMA) is frequently overexpressed in nonprostate malignancies. This preclinical study investigated the molecular basis of the application of PMSA-targeting radiopharmaceuticals in breast cancer subtypes. <b>Methods:</b> The somatic copy number status and the transcriptomic and protein expressions of <i>FOLH1</i> (gene name of PSMA) were analyzed across breast cancer subtypes in 998 patients from The Cancer Genome Atlas dataset. <b>Results:</b> <i>FOLH1</i> was frequently amplified in basallike breast cancer (BLBC) (32%) compared with luminal and human epidermal growth factor receptor 2-positive subtypes (16% and 17%, respectively; <i>P</i> < 0.01). <i>FOLH1</i> expression was higher in BLBC (<i>P</i> < 0.001) and was negatively correlated with estrogen-receptor and progesterone-receptor expressions. Consistently, the PSMA protein level was higher in BLBC (<i>P</i> < 0.05). Interestingly, <i>FOLH1</i> expression was associated with relapse-free and distant metastasis-free survival in patients with BLBC. <b>Conclusion:</b> The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype.