P2.16 Estrogen Receptors Alpha and Beta as Targets for Non-Small Cell Lung Cancer Hormonal Therapy

Abstract

ABSTRACT Background Recent investigations demonstrate important role of estrogens in occurrence and progression of non-small cell lung cancer (NSCLC) as well as prognostic value of estrogen receptors (ER) alpha and beta in the tumor tissue. But the data about ER expression in the NSCLC differ significantly because of using semiquantitative methods for estimation only. To answer the question what is the significance of each type of the receptor as potential targets for antiestrogen therapy we have studied ERalpha and ERbeta expression in the NSCLC using the quantitative immunofluorescence methodology developed previously. Materials and methods NSCLC surgical specimens (97) were analyzed by flowcytometry. Primary antibodies were: anti-ERbeta 14C8, mouse IgG2a and IgG1 (Abcam); anti-ERalpha 1D5 (DAKO). Secondary antibody - FIT?-conjugated anti-mouse-IgG (F2772,Sigma). Number of specifically fluorescent cells was analyzed with Kolmogorov-Smirnov statistical approach. Three levels of ERbeta expression were compared: high - more than 50 % of the specifically fluorescent cells; moderate - 30-49 %; low - less than 30 %. Results 1.Expression of ERalpha and beta was reviled in about 90 % of NSCLC specimens. 2.Median of ERalpha level (22 %) was in 1·7-fold less then ERbeta level (37 %, p = 0,000002). 3.In women median of ERbeta level, but not ERalpha, was in 1·6-fold higher than in men (p = 0,008). 4.ERbeta level in men (32 %) and women (50 %) was higher in adenocarcinomas as compared with squamous-cell carcinomas in men (28 %): p = 0,0001 and 0,013 respectively. 5.ERalpha level in men (27 %) and women (22 %) was higher in adenocarcinomas as compared with squamous-cell carcinomas in men (16 %): p = 0,0003 and 0,016 respectively. 6. High and moderate level of ERbeta was revealed in 61 % of cases, while ERalpha - in 28 % only. 7. It was no coexpression of high ERalpha with low ERbeta level or any ERalpha expression with no ERbeta. Conclusion NSCLC is characterized by expression of ERbeta and ERalpha that is higher in adenocarcinomas than in squamous-cell carcinomas. ERbeta have main clinical relevance as potential target for antiestrogen therapy, because of higher level and frequency of expression than ERalpha. Generally, about half of adenocarcinoma and one third of squamous-cell carcinoma patients could benefit from adjuvant antiestrogen therapy. Supported by RFBR (Grants 10-04-00551-?,12-04-00028-?).