Elevated ESR2 and BRCA1 gene expression in adenomyosis associated with endometrial cancer: a pilot study

Adenomyosis is a benign uterine disease that has been associated with endometrial proliferative disorders. Adenomyosis and endometrial cancer (EC) are sex-steroid-dependent conditions that may coexist, but their estrogen receptor (ER) and progesterone receptor (PR) signaling landscape is poorly defined. The present multicenter study aimed to characterize the expression of estrogen (ESR1/ESR2 plus the coregulators NCOA1, CCND1, BRCA1) and progesterone (PGR plus FOXO1, and CYP26A1) receptor pathway-related genes in hysterectomy specimens of patients with adenomyosis and coexisting EC. Specimens from three groups of patients (n = 10 per group) referred to two tertiary hospitals were studied: adenomyosis plus EC (Group 1), only adenomyosis (Group 2), and only EC (Group 3). Gene expression was assessed by droplet digital PCR using a compartment-matched design. Analysis was compartment-specific, and no cross-compartment comparisons were performed. Compared with isolated adenomyosis, adenomyotic lesions from uteri with coexisting EC showed higher ESR2 (p = 0.0082) and BRCA1 (p = 0.0007) expression, with no differences in ESR1, NCOA1, or CCND1. PR-related gene expression (PGR, FOXO1, and CYP26A1) did not differ between adenomyosis groups. Although preliminary, the present findings indicate that adenomyosis coexisting with EC is characterized by elevated expression of ESR2 and BRCA1, suggesting an enriched ER-related microenvironment that may be relevant to local estrogen responsiveness.