Department of Pathology, Medical School, University of Athens, and Department of Breast Cancer Surgery, Blue Cross Hospital, str Patriarchou Grigoriou E 17 Ag Paraskevi Attiki, 15341, Athens, Greece.
Med Oncol. 2011 Dec;28(4):934-40. doi: 10.1007/s12032-010-9554-8. Epub 2010 May 11.
Estrogen receptor alpha-encoded by ESR1 gene-overexpression correlates with prognosis and response to specific chemotherapy in breast adenocarcinoma cases. Mechanisms of ESR-1 deregulation in carcinomas remain under investigation. To analyze ESR1 in carcinomas of different histogenesis. Using tissue microarray technology, 172 primary carcinomas including breast ductal adenocarcinomas (n=60), hepatocellular carcinomas (n=52), and colon adenocarcinomas (n=60) were cored and re-embedded in three paraffin blocks. Initial diagnosis was based on liquid based cytology (LiquiPrep/ThinPrep). Immunohistochemistry and fluorescence in situ hybridization were performed. Quantitative evaluation of ER-a protein levels was assessed by applying digital image analysis. ER-a overexpression was observed in 41/60 (68.3%), 23/52 (44.2%) and 4/60 (6.6%) cases, respectively. ESR1 gene multiple copies were confirmed in 13/60 (21.6%) breast adenocarcinomas, but high amplification only in 8/13 (62.8%). Allelic absence was identified in 3/52 (5.7%) hepatocellular carcinomas, whereas colon adenocarcinomas demonstrated gene gains in 5/60 (8.3%) cases referred to chr 6 aneuploidy and not to amplification. ER-a overall expression was associated strongly to ESR1 gene copies only in breast carcinoma (P=0.036). ESR-1 gene overexpression happens frequently in breast cancer, but only a subset of them are high amplified cases correlated to increased response rates in hormonal therapy (tamoxifen). Absence of this mechanism in hepatocellular and colon carcinomas maybe is a negative factor for applying this therapy. This is a pattern of histo-genetic depended targeted therapeutic strategy.
雌激素受体α由 ESR1 基因过表达编码，与乳腺腺癌病例的预后和对特定化疗的反应相关。癌中 ESR-1 失调的机制仍在研究中。分析不同组织发生的癌中的 ESR1。使用组织微阵列技术，对包括乳腺导管腺癌（n=60）、肝细胞癌（n=52）和结肠腺癌（n=60）在内的 172 例原发性癌进行芯活检并重新嵌入三个石蜡块中。最初的诊断基于液体基细胞学（LiquiPrep/ThinPrep）。进行免疫组织化学和荧光原位杂交。通过应用数字图像分析评估 ER-a 蛋白水平的定量评估。分别在 41/60（68.3%）、23/52（44.2%）和 4/60（6.6%）的病例中观察到 ER-a 过表达。在 13/60（21.6%）例乳腺腺癌中证实了 ESR1 基因多个拷贝，但仅在 8/13（62.8%）的高扩增中。在 3/52（5.7%）例肝细胞癌中鉴定出等位基因缺失，而结肠腺癌在 5/60（8.3%）例中表现出基因增益，与染色体 6 非整倍体有关，而不是扩增。ER-a 的总体表达仅在乳腺癌中与 ESR1 基因拷贝强烈相关（P=0.036）。ESR-1 基因过表达在乳腺癌中经常发生，但只有一小部分是与激素治疗（他莫昔芬）增加反应率相关的高扩增病例。在肝细胞癌和结肠腺癌中缺乏这种机制可能是应用这种治疗的一个负面因素。这是一种基于组织发生的靶向治疗策略模式。
