Zhou Hui-Hui, Liu Li-Yan, Yu Guo-Hua, Qu Gui-Mei, Gong Pei-You, Yu Xiao, Yang Ping
Department of Pathology, Yuhuangding Hospital of Qingdao University, Yantai, P.R. China.
Department of Medicine, The fifth People's Hospital of Jinan, Jinan, P.R. China.
Anticancer Res. 2017 Aug;37(8):4529-4537. doi: 10.21873/anticanres.11850.
Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis.
The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas.
Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74.36% and 69.23%.
BNEC is one of the most malignant tumors with severe invasiveness and poor prognosis. Immunohistochemistry revealed that CD56, Syn, CgA, NSE, TTF-1, CK, CK7, CK20, P63, HMB45, S-100 protein and LCA immune markers play important roles in diagnosis and differentiation. Many factors, including the patient's age, size and shape of the tumor, operative method, perineuronal invasion, vascular invasion, distant organ metastasis and pathological type, show great difference in influencing OS time of patients, among which the size of the tumor, no invasion, vascular invasion and distant organ metastasis are independent risk factors affecting prognosis (survival time). Radical cystectomy is the prior alternative to treat this tumor.
通过分析和总结膀胱神经内分泌癌（BNEC）患者的临床病理特征、免疫组化表达、病理诊断标准、预后等因素，更好地了解BNEC，为临床病理和预后提供有力依据。
回顾性分析39例BNEC患者的临床病理资料，并进行长达5年的随访（中位随访时间=650天），随访基于免疫组化染色。采用Kaplan-Meier法进行生存分析，并用对数秩检验。采用多因素Cox回归分析筛选影响患者生存的独立危险因素。在这39例BNEC患者中，男性26例，女性13例，男女比例为2:1。发病年龄在44至86岁之间，中位年龄为62岁，平均年龄为61.97岁。组织学上，参照世界卫生组织神经内分泌肺肿瘤分类标准，典型类癌7例，非典型类癌8例，小细胞癌12例，大细胞癌12例。这些病例中，有11例为特征性尿路上皮癌，9例为腺癌。
免疫组化染色显示，在这39例BNEC中，神经内分泌标志物的阳性表达，包括神经细胞黏附分子56（CD56）、突触素（Syn）、嗜铬粒蛋白A（CgA）、神经元特异性烯醇化酶（NSE）、甲状腺转录因子-1（TTF-1）、细胞角蛋白（CK）和细胞角蛋白7（CK7），分别占39/39、27/39、18/39、39/39、19/39、10/39和8/39。相比之下，细胞角蛋白20（CK20）、蛋白63（P63）、人黑素瘤黑色45（HMB45）、S-100蛋白（S-100）和白细胞共同抗原（LCA）均呈阴性表达。随访期间，12例患者死亡。1年、3年和5年总生存率（OS）分别为76.92%、74.36%和69.23%。
BNEC是侵袭性最强、预后最差的恶性肿瘤之一。免疫组化显示，CD56、Syn、CgA、NSE、TTF-1、CK、CK7、CK20、P63、HMB45、S-100蛋白和LCA免疫标志物在诊断和鉴别中起重要作用。许多因素，包括患者年龄、肿瘤大小和形态、手术方式、神经侵犯、血管侵犯、远处器官转移和病理类型，在影响患者OS时间方面差异很大，其中肿瘤大小、无侵犯、血管侵犯和远处器官转移是影响预后（生存时间）的独立危险因素。根治性膀胱切除术是治疗该肿瘤的首选方法。
