Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors.
Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors.
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发表时间：
2001-03
期刊：
影响因子：
11.2
通讯作者：
P. Roger;M. Sahla;S. Mäkelä;J. Gustafsson;P. Baldet;H. Rochefort
中科院分区：
文献类型：
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作者：
P. Roger;M. Sahla;S. Mäkelä;J. Gustafsson;P. Baldet;H. Rochefort
为了了解雌激素受体β (ERbeta)在乳腺癌发生中的意义，我们评估了ERbeta在侵袭前乳腺肿瘤中的表达。通过定量免疫组织化学，使用图像分析仪对118例患者（71例为良性乳腺疾病（BBD）， 59例为原位癌（CIS））的130个不同组织学风险的病变进行erβ阳性上皮细胞或肿瘤细胞的百分比检测，并与118个相邻组织学正常腺体进行比较。研究了五组浸润性癌风险增加的病变，从无增生的BBD到高级别CIS。结果与erα和Ki67免疫染色比较。erβ阳性细胞的百分比在“正常”乳腺和非增殖性BBD中较高（中位数为85%），在无异型性的增殖性BBD和CIS中显著降低（P < 0.0001），而erα水平呈反比进展。在正常乳腺中，ERbeta水平不随周围病变的性质而变化，并且显著高于邻近的浸润前病变（P < 0.007），但非增散性BBD除外。增殖性BBD中erβ水平下降，预测erα升高，这在非典型性BBD中是显著的。在高级别导管原位癌中，两种ER水平均较低。erβ和erα的比值在正常腺体中较高，在增生性病变中显著降低。ERbeta染色与Ki67呈负相关（r = -0.333; P < 0.001），尤其在高级别导管原位癌中（r = -0.57; P < 0.02）。与细胞增殖的其他标准相关的ERbeta蛋白水平的显著和早期下降表明ERbeta对乳腺癌前病变中雌激素的有丝分裂活性具有保护作用。了解每个侵入前病变中erβ和erα的含量有助于合理地针对每个患者进行抗雌激素预防治疗。
To understand the significance of estrogen receptor beta (ERbeta) in mammary carcinogenesis, we evaluated the expression of ERbeta in preinvasive mammary tumors. The percentage of ERbeta-positive epithelial or tumoral cells was assayed by quantitative immunohistochemistry using an image analyzer in 130 lesions of varying histological risk from 118 patients [71 with benign breast disease (BBD) and 59 with carcinoma in situ (CIS)] and compared with 118 adjacent histologically normal glands. Five groups of lesions with an increasing risk of invasive cancer, from BBD without hyperplasia to high-grade CIS, were studied. Results were compared with ERalpha and Ki67 immunostaining. The percentage of ERbeta-positive cells was high (median, 85%) in "normal" mammary glands and in nonproliferative BBD and decreased significantly (P < 0.0001) in proliferative BBD without atypia and in CIS, contrasting with an inverse progression for the ERalpha level. In normal mammary glands, the ERbeta level did not vary according to the nature of the lesion at the periphery and was significantly higher (P < 0.007) than in adjacent preinvasive lesions, except in nonproliferative BBD. The ERbeta level decreased in proliferative BBD, anticipating the ERalpha increase, which was significant in BBD with atypia. In high-grade ductal carcinoma in situ, both ER levels were low. The ratio between ERbeta and ERalpha was high in normal glands, and decreased significantly in proliferative lesions. ERbeta staining was inversely correlated with Ki67 (r = -0.333; P < 0.001), more particularly in high-grade ductal carcinoma in situ (r = -0.57; P < 0.02). The marked and early decreased level of ERbeta protein associated with other criteria of cell proliferation suggests a protective effect of ERbeta against the mitogenic activity of estrogens in mammary premalignant lesions. Knowledge of the ERbeta and ERalpha content in each preinvasive lesion should help to rationalize antiestrogen preventive therapy adapted to each individual patient.