Quantitative analysis of estrogen receptor-α and-β messenger RNA expression in breast carcinoma by real-time polymerase chain reaction

Abstract

BACKGROUND. Estrogen action is mediated not only through a classic estrogen receptor (ER) (ER-α) but also through a second ER (ER-β) that has a structure and function similar to ER-α. A correlation between ER-β mRNA expression with ER and progesterone receptor (PR) protein levels as well as prognostic factors remains to be established in breast carcinoma. METHODS. The authors conducted a quantitative analysis of ER-α and ER-β mRNA expression in 116 breast tumors using real-time polymerase chain reaction (PCR), and investigated a possible correlation between ER-α and ER-β mRNA expression and ER and PR status as determined by enzyme immunoassay as well as with various prognostic factors. RESULTS. ER-α mRNA levels were significantly (P < 0.01) higher in ER positive compared with ER negative tumors. Conversely, ER-β mRNA levels were significantly (P < 0.01) lower in ER positive compared with ER negative tumors. Accordingly, the ratio of ER-β to ER-α was significantly (P < 0.01) higher in ER negative compared with ER positive tumors. A subset analysis based on ER and PR status showed that ER-β mRNA levels as well as the ratios of ER-β to ER-α mRNA level were highest in ER negative and PR negative tumors (P < 0.05). ER-α mRNA levels were significantly (P < 0.05) higher in postmenopausal compared with premenopausal tumors. Histologic Grade 3 tumors showed a significant decrease in ER-α mRNA levels compared with Grade 1 and 2 tumors (P < 0.01 and P < 0.05, respectively). No significant correlation between ER-α and ER-β mRNA levels and histologic type, tumor size, or lymph node status was observed. CONCLUSIONS. An absolute and relative increase in ER-β mRNA levels in ER negative and PR negative breast tumors, which rarely respond to endocrine therapy, suggests the possible involvement of up-regulation of ER-β mRNA in the development of estrogen-independent tumors. (C) 2000 American Cancer Society.