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

BACKGROUND. Estrogen action is mediated not only through a classic estrogen receptor (ER) (ER-alpha) but also through a second ER (ER-beta) that has a structure and function similar to ER-alpha. A correlation between ER-beta mRNA expression with ER and progesterone receptor (PR) protein levels as we ll as prognostic factors remains to be established in breast carcinoma. METHODS, The authors conducted a quantitative analysis of ER-alpha and ER-P beta mRNA expression in 116 breast tumors using real-time polymerase chain reaction (PCR), and investigated a possible correlation between ER-alpha a nd ER-beta mRNA expression and ER and PR status as determined by enzyme imm unoassay as well as with various prognostic factors. RESULTS. ER-alpha mRNA levels were significantly (P < 0.01) higher in ER po sitive compared with ER negative tumors. Conversely, ER-beta mRNA levels we re significantly (P < 0.01) lower in ER positive compared with ER negative turners. Accordingly, the ratio of ER-beta to ER-alpha was significantly (P < 0.01) higher in ER negative compared with ER positive tumors. A subset a nalysis based on ER and PR status showed that ER-beta mRNA levels as well a s the ratios of ER-beta to ER-alpha mRNA level were highest in ER negative and PR negative tumors (P < 0.05). ER-alpha mRNA levels were significantly (P < 0.05) higher in postmenopausal compared with premenopausal tumors. His tologic Grade 3 tumors showed a significant decrease in ER-alpha mRNA level s compared with Grade 1 and 2 tumors (P < 0.01 and P < 0.05, respectively). No significant correlation between ER-alpha and ER-alpha mRNA levels and h istologic type, tumor size, or lymph node status was observed. CONCLUSIONS. An absolute and relative increase in ER-beta 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-beta mRNA in the development of estrogen-independent tumors. Cancer 2000;89:1732-8. (C) 2000 American Cancer Society.