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雌激素受体β2 在增生性和非浸润性乳腺肿瘤病变中与 Ki-67 呈负相关。

Estrogen receptor β2 is inversely correlated with Ki-67 in hyperplastic and noninvasive neoplastic breast lesions.

机构信息

Laboratory of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str, Goudi, 11527, Athens, Greece.

出版信息

J Cancer Res Clin Oncol. 2014 Jun;140(6):1057-66. doi: 10.1007/s00432-014-1652-0. Epub 2014 Mar 27.

Abstract

PURPOSE

The purpose of the study is to compare expression levels of ΕRα, ERβ1, ERβ2 and cell proliferation marker Ki-67 in normal breast and hyperplastic and noninvasive neoplastic breast lesions.

MATERIALS AND METHODS

Routinely processed breast tissue from 55 patients provided 65 cases of noninvasive lesions, namely, epithelial hyperplasia of usual type (HUT), apocrine metaplasia (AM), atypical hyperplasia (AH) and ductal carcinoma in situ (DCIS) and 14 cases of adjacent normal breast tissue. Expression of ERα, ERβ1 and ERβ2 were evaluated using immunohistochemistry and correlated with Ki-67 labeling index (Ki-67 LI) and menopausal status of the patients.

RESULTS

Compared with normal breast, ERα expression increased in low to intermediate-grade DCIS (DCIS1/2) and tended to decrease in high-grade DCIS, while ERβ1 expression decreased in DCIS irrespective of grade. Mean Ki-67 LI in HUT, low to intermediate-grade DCIS and high-grade DCIS was higher than in normal breast. Higher than normal Ki-67 LI correlated with low ERβ2 expression in the whole set of cases and with high ERα expression and low ERβ2 expression in the postmenopausal cases of the subset that is generated by excluding AM and high-grade DCIS. Postmenopausal status correlated with low ERβ1 expression in the whole set and with higher than normal Ki-67 LI, high ERα expression and low ERβ1 expression in the subset.

CONCLUSIONS

These findings are in accordance with an ERα-opposing oncosuppressive role of ERβ2 in mammary carcinogenesis along the HUT-AH-DCIS1/2 pathway.

摘要

目的

本研究旨在比较正常乳腺、增生性和非浸润性肿瘤性乳腺病变中 ΕRα、ERβ1、ERβ2 和细胞增殖标志物 Ki-67 的表达水平。

材料和方法

从 55 例患者的常规处理的乳腺组织中获得 65 例非浸润性病变,即普通型上皮增生(HUT)、大汗腺化生(AM)、不典型增生(AH)和导管原位癌(DCIS),以及 14 例相邻正常乳腺组织。采用免疫组织化学法检测 ERα、ERβ1 和 ERβ2 的表达,并与患者的绝经状态及 Ki-67 标记指数(Ki-67 LI)相关联。

结果

与正常乳腺相比,低-中级别 DCIS(DCIS1/2)中 ERα 表达增加,而高级别 DCIS 中 ERα 表达减少,而 ERβ1 表达在 DCIS 中无论级别高低均减少。HUT、低-中级别 DCIS 和高级别 DCIS 的平均 Ki-67 LI 均高于正常乳腺。在整个病例组中,高于正常的 Ki-67 LI 与 ERβ2 表达降低相关,在排除 AM 和高级别 DCIS 后,在由绝经后病例组成的亚组中,与高 ERα 表达和低 ERβ2 表达相关。在整个病例组中,绝经后状态与 ERβ1 表达降低相关,在亚组中与高于正常的 Ki-67 LI、高 ERα 表达和低 ERβ1 表达相关。

结论

这些发现与 ERβ2 在 HUT-AH-DCIS1/2 途径中对 ERα 起拮抗作用的抑癌作用一致。

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