Bonkhoff H, Fixemer T, Hunsicker I, Remberger K
Institute of Pathology, University of the Saarland, Homburg/Saar, Germany.
Am J Pathol. 1999 Aug;155(2):641-7. doi: 10.1016/S0002-9440(10)65160-7.
Estrogens have been implicated in prostatic cancerogenesis and tumor progression. The mechanisms underlying estrogen signaling in human prostate tissue, however, remain poorly understood. Using immunohistochemical and in situ hybridization (ISH) techniques, the present study demonstrates the classical estrogen receptor (ERalpha) in premalignant lesions and prostatic adenocarcinoma through the various stages of the disease. Conversely, the novel characterized ERbeta subtype was undetectable in human prostate tissue. High-grade prostatic intraepithelial neoplasia revealed ERalpha mRNA and protein expression in 28% and 11% of cases evaluated. Focal ER immunoreactivity was detected in a minority of low- to intermediate-grade adenocarcinoma. High-grade (primary Gleason grade 4 and 5) tumors revealed ER protein expression in 43% (62% respectively) of cases. The most significant ERalpha gene expression on mRNA and protein levels was observed in hormone refractory tumors and metastatic lesions, including lymph node and bone metastases. Results of the current study suggest that estrogens can affect prostatic cancerogenesis and neoplastic progression through an ER-mediated process in human prostate tissue.
雌激素与前列腺癌的发生及肿瘤进展有关。然而，人类前列腺组织中雌激素信号传导的潜在机制仍知之甚少。本研究采用免疫组织化学和原位杂交（ISH）技术，在疾病的各个阶段，在癌前病变和前列腺腺癌中证实了经典雌激素受体（ERα）的存在。相反，在人类前列腺组织中未检测到新发现的ERβ亚型。在评估的病例中，高级别前列腺上皮内瘤变分别在28%和11%的病例中显示出ERα mRNA和蛋白表达。在少数低至中级腺癌中检测到局灶性ER免疫反应性。高级别（原发性Gleason分级4和5）肿瘤在43%（分别为62%）的病例中显示出ER蛋白表达。在激素难治性肿瘤和转移灶，包括淋巴结和骨转移中，观察到ERα基因在mRNA和蛋白水平上最显著的表达。本研究结果表明，雌激素可通过人类前列腺组织中ER介导的过程影响前列腺癌的发生和肿瘤进展。
