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浙江大学学报（医学版）
浙江大学学报（医学版）  2016, Vol. 45 Issue (1): 24-30    DOI: 10.3785/j.issn.1008-9292.2016.01.04
神经内分泌肿瘤专题     
神经内分泌分化在胃腺癌进展及患者预后中的意义
徐芳英1, 刘琴1, 韩丰艳1, 徐恩萍1, 来茂德1, 赵仲生2
1. 浙江大学医学院基础医学院浙江省蛋白质组学重点实验室, 浙江 杭州 310058;
2. 浙江省人民医院病理科, 浙江 杭州 310014
Association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma
XU Fangying1, LIU Qin1, HAN Fengyan1, XU Enping1, LAI Maode1, ZHAO Zhongsheng2
1. Key Laboratory of Disease Proteomics of Zhejiang Province, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China;
2. Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
全文: PDF(971 KB)  
摘要: 

目的:研究胃腺癌伴神经内分泌分化现象与肿瘤进展及患者预后的关系。方法:收集了240例胃腺癌患者石蜡包块,并制备组织芯片,同时调查患者临床病理信息及随访信息。运用免疫组织化学染色法检测嗜铬素A、突触素和促泌素的表达情况,统计分析其表达与临床病理指标及患者预后的关系。结果:嗜铬素A与患者年龄、性别和肿瘤部位、Lauren分型、组织学分化程度、浸润深度、淋巴结转移、远处转移及TNM分期均无相关性;突触素阳性时肿瘤浸润深度较深(P=0.042);促泌素阳性时发生淋巴结转移者更多(P=0.047)。单因素生存分析结果提示,在胃腺癌弥漫型患者中嗜铬素A阳性(P=0.019)或促泌素阳性(P=0.001)时预后较差,而突触素的表达(P=0.102)与预后无关。TNM分期Ⅱ期患者中,嗜铬素A阳性(P=0.049)和突触素阳性(P=0.002)是不利预后因素,但是促泌素与预后无关(P=0.529),而且Cox比例风险模型分析显示突触素是患者独立的预后指标。结论:嗜铬素A、突触素与促泌素虽然都是神经内分泌标志物,但临床意义不尽相同;胃腺癌伴神经内分泌分化时,肿瘤浸润深度较深,更易发生淋巴结转移,患者预后较差。
关键词 ： 神经分泌系统/病理学,  胃肿瘤/病理学,  腺癌/病理学,  嗜铬粒蛋白质A,  突触囊泡蛋白,  生长激素,  预后    
Abstract：

Objective: To investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma. Methods: Clinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed. Results: The expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival. Conclusion: Neuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.
Key words： Neurosecretory systems/pathology    Stomach neoplasms/pathology    Adenocarcinoma/pathology    Chromogranin A    Synaptophysin    Growth hormone    Prognosis
收稿日期: 2015-12-10     
CLC:  R73  
基金资助:

浙江省科技计划项目(2012C13014-3)
通讯作者: 来茂德(1960-),男,博士,教授,博士生导师,主要从事大肠癌病理学研究;赵仲生(1950-),男,硕士,主任医师,博士生导师,主要从事胃癌的发病机制及预后研究     E-mail: lmd@zju.edu.cn;zhaozhongsheng1950@163.com
作者简介: 徐芳英(1974-),女,博士,副教授,硕士生导师;主要从事肿瘤的分子生物学机制及预后研究;E-mail:xfy@zju.edu.cn;http://orcid.org/0000-0001-6074-3234
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徐芳英 等. 神经内分泌分化在胃腺癌进展及患者预后中的意义[J]. 浙江大学学报（医学版）, 2016, 45(1): 24-30.
XU Fangying, LIU Qin, HAN Fengyan, XU Enping, LAI Maode, ZHAO Zhongsheng. Association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma. Journal of ZheJiang University(Medical Science), 2016, 45(1): 24-30.

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http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.01.04      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I1/24

[1] BUSMAN F T, CANNIER F, HUMAN R H, et al. WHO Classifictation of Tumours of the Digestive system[M]. 4th ed. Lyon:International Agency for Research on Cancer, 2010:45-80.
[2] JIANG S X, MIKAMI T, UMEZAWA A, et al. Gastric large cell neuroendocrine carcinomas:a distinct clinicopathologic entity[J]. Am J Surg Pathol, 2006, 30(8):945-953.
[3] KUBOTA T, OHYAMA S, HIKI N, et al. Endocrine carcinoma of the stomach:clinicopathological analysis of 27 surgically treated cases in a single institute[J]. Gastric Cancer, 2012, 15(3):323-330.
[4] WANG L L, YAO G Y, ZHAO Z S, et al. Clonality analysis of neuroendocrine cells in gastric adenocarcinoma[J]. World J Gastroenterol, 2013, 19(32):5340-5346.
[5] WAGNER L, TEMPLE E, REINING G, et al. Culture of human insulinoma cells:development of a neuroendocrine tumor celland human pancreatic islet cell-specific monoclonal antibody[J]. J Endocrinol, 1998, 156(3):469-476.
[6] EREN F, CELIKEL C, GVLLVOLU B. Neuroendocrine differentiation in gastric adenocarcinomas; correlation with tumor stage and expression of VEGF and p53[J]. Pathol Oncol Res, 2004, 10(1):47-51.
[7] MARTINSEN T C, SKOGAKER N E, FOSSMARK R, et al. Neuroendocrine cells in diffuse gastric carcinomas:an ultrastructural study with immunogold labeling of chromogranin A[J]. Appl Immunohistochem Mol Morphol, 2010, 18(1):62-68.
[8] YAO G Y, ZHOU J L, LAI M D, et al. Neuroendocrine markers in adenocarcinomas:an investigation of 356 cases[J]. World J Gastroenterol, 2003, 9(4):858-861.
[9] WANG K L, YANG Q, CLEARY K R, et al. The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation[J]. Cancer, 2006, 107(7):1467-1474.
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