Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
J Gastroenterol. 2019 Sep;54(9):819-828. doi: 10.1007/s00535-019-01570-0. Epub 2019 Mar 12.
The prognostic importance of the neuroendocrine (NE) markers involving neural cell adhesion molecule (NCAM) has been unclear enough to be adopted for WHO classification in patients with pancreatic neuroendocrine neoplasms (Pan-NENs). This study aimed to elucidate whether the three NE markers such as chromogranin A, synaptophysin, and NCAM decide prognoses for patients with well-differentiated tumors.
Between April 2002 and October 2018, 217 patients were included in this study. Tissue samples from tumors of Pan-NENs were immunochemically stained for the aforementioned NE markers. Diffuse and intense staining was defined as positive, while faint or focal staining and non-staining were considered negative.
The median age of patients was 55 years. The median observation period was 1415 days. In multivariate analysis of progression-free survival (PFS), liver metastasis, Ki-67 index, and triple-positive staining of NE markers were risk factors. The 5-year PFS rate of patients with and without triple-positive NE markers was 56.3% and 23.8%, respectively (P < 0.0001). In multivariate analysis of overall survival (OS), R0 resection, Ki-67 index and triple-positive NE markers (hazard ratio 0.4, P = 0.02) were the risk factors. The 5-year OS rate of patients with and without triple-positive NE markers was 88.8% and 66.4%, respectively (P = 0.014). The tumors of patients without triple-positive NE markers were associated with large tumor size, a high mitotic rate and high Ki-67 index.
Triple-positive NE marker staining was a simple and practical indicator of prognoses in patients with well-differentiated Pan-NETs.
神经内分泌（NE）标志物中涉及神经细胞黏附分子（NCAM）的预后意义尚不清楚，足以被纳入世界卫生组织（WHO）对胰腺神经内分泌肿瘤（Pan-NENs）的分类标准。本研究旨在阐明三种 NE 标志物（嗜铬粒蛋白 A、突触素和 NCAM）是否决定了分化良好肿瘤患者的预后。
本研究纳入了 217 名患者，纳入时间为 2002 年 4 月至 2018 年 10 月。对 Pan-NENs 肿瘤组织样本进行上述 NE 标志物的免疫化学染色。弥漫性和强染色定义为阳性，而弱或局灶性染色和非染色则定义为阴性。
患者的中位年龄为 55 岁，中位观察期为 1415 天。在无进展生存期（PFS）的多变量分析中，肝转移、Ki-67 指数和三重阳性 NE 标志物是危险因素。有和没有三重阳性 NE 标志物的患者的 5 年 PFS 率分别为 56.3%和 23.8%（P<0.0001）。在总生存期（OS）的多变量分析中，R0 切除、Ki-67 指数和三重阳性 NE 标志物（危险比 0.4，P=0.02）是危险因素。有和没有三重阳性 NE 标志物的患者的 5 年 OS 率分别为 88.8%和 66.4%（P=0.014）。没有三重阳性 NE 标志物的患者的肿瘤与较大的肿瘤大小、高有丝分裂率和高 Ki-67 指数相关。
三重阳性 NE 标志物染色是预测分化良好的 Pan-NET 患者预后的一种简单实用的指标。
