Department of Clinical and Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, Turin, Italy.
Virchows Arch. 2012 Apr;460(4):415-21. doi: 10.1007/s00428-012-1223-1. Epub 2012 Mar 16.
Neuroendocrine (NE) breast carcinoma is defined by morphological features similar to those of NE tumors of other organs and NE marker expression in at least 50 % of neoplastic cells. However, a NE morphology may be observed even in breast carcinomas lacking NE markers. Human achaete-scute homolog-1 (hASH-1) is a transcription factor that plays a key role in the regulation of mammalian neural and NE cell development and has been identified in several human NE tumors. The aim of this study was to investigate hASH-1 expression in human breast cancers. hASH-1 expression was evaluated in 482 consecutive non-NE invasive breast carcinomas, in a series of 84 breast cancers with >50 % NE marker expression (high NE differentiation) and 21 carcinomas with NE histology but negative or focally (<50 %) positive for NE markers (low NE differentiation). hASH-1 protein was evaluated by a specific monoclonal antibody using immunohistochemistry and gene expression by real-time polymerase chain reaction. None of the non-NE invasive breast carcinomas expressed hASH-1 at any levels. hASH-1 was expressed in tumor cell nuclei of 63 and 38 % of cases with high and low NE differentiation, respectively. Strong correlation with protein and gene expression levels was observed (p < 0.0001). hASH-1 expression was correlated to a low mitotic count (p = 0.02) and a low Ki67 proliferative index (p = 0.0062). hASH-1 expression occurs in breast cancers with NE differentiation regardless of the extent of the NE cell population, and it is restricted to a subset of tumor cells having a low proliferative potential.
神经内分泌（NE）乳腺癌的定义为形态学特征类似于其他器官的 NE 肿瘤，并且至少 50%的肿瘤细胞表达 NE 标志物。然而，即使在缺乏 NE 标志物的乳腺癌中也可能观察到 NE 形态。人类同源盒基因 1（hASH-1）是一种转录因子，在调节哺乳动物神经和 NE 细胞发育中发挥关键作用，已在几种人类 NE 肿瘤中得到鉴定。本研究旨在研究 hASH-1 在人类乳腺癌中的表达。评估了 482 例连续的非 NE 浸润性乳腺癌、84 例 NE 标志物表达>50%（高 NE 分化）的乳腺癌系列和 21 例具有 NE 组织学但 NE 标志物阴性或局灶性（<50%）阳性的乳腺癌的 hASH-1 表达。使用免疫组织化学和实时聚合酶链反应评估 hASH-1 蛋白表达。在任何水平均未检测到非 NE 浸润性乳腺癌中表达 hASH-1。在高 NE 分化和低 NE 分化的病例中，分别有 63%和 38%的病例肿瘤细胞核中表达 hASH-1。观察到与蛋白和基因表达水平的强相关性（p<0.0001）。hASH-1 表达与低有丝分裂计数（p=0.02）和低 Ki67 增殖指数（p=0.0062）相关。hASH-1 表达发生在具有 NE 分化的乳腺癌中，无论 NE 细胞群体的范围如何，并且仅局限于具有低增殖潜能的肿瘤细胞亚群。
