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胃肠胰神经内分泌肿瘤中的癌基因表达:对发病机制的影响

Oncogene expression in gastroenteropancreatic neuroendocrine tumors: implications for pathogenesis.

作者信息

Wang D G, Johnston C F, Buchanan K D

机构信息

Division of Metabolism and Endocrinology, School of Clinical Medicine, The Queen's University of Belfast, United Kingdom.

出版信息

Cancer. 1997 Aug 15;80(4):668-75.

PMID:9264349
Abstract

BACKGROUND

Neuroendocrine tumors of the gastroenteropancreatic system include pancreatic islet cell and carcinoid tumors. These tumors comprise a functionally and biologically heterogeneous group of neoplasms that rarely show reliable histopathologic signs of malignancy. No etiologic factors are proven to be associated with them, and their exact ontogeny and carcinogenesis remain unknown.

METHODS

Monoclonal antibodies were employed, along with microwave antigen retrieval and the avidin-biotin immunohistochemical method, to investigate the expression of c-myc, bcl-2, c-erb B-2, c-erb B-3, c-jun, and proliferating cell nuclear antigen (PCNA) in a retrospective series of 116 primary gastroenteropancreatic neuroendocrine tumors (GPNTs). The authors attempted to correlate this expression with the clinicopathologic outcome of the disease.

RESULTS

Immunoreactivities for c-myc, bcl-2, c-erb B-2, c-erb B-3, and c-jun were detected in 100%, 45%, 24%, 7%, and 24% of pancreatic neuroendocrine tumors (PNTs), respectively. In carcinoid tumors, immunoreactivities were detected for c-myc (63%), bcl-2 (28%), c-erb B-2 (31%), c-erb B-3 (6%), and c-jun (23%). There were significantly higher incidences of c-myc, bcl-2, and c-erb B-2 immunoreactivities in carcinoid tumors of the rectum than in those of the appendix, and significantly higher incidences of bcl-2 and c-jun immunoreactivities in carcinoid tumors of the bronchus than in those of the appendix. Incidence of PCNA immunoreactivity was significantly higher in malignant than in benign PNTs and also significantly higher in carcinoid tumors of the jejunum and ileum than in those of the appendix.

CONCLUSIONS

The oncogenes c-myc, bcl-2, c-erb B-2, and c-jun are frequently expressed in human GPNTs. The expression of these oncogenes may represent pathogenic events in the generation, malignant transformation, and progression of GPNTs. The immunohistochemical evaluation of cell kinetics in GPNTs by PCNA might be a useful adjunct to conventional diagnostic procedures.

摘要

背景

胃肠胰系统神经内分泌肿瘤包括胰岛细胞瘤和类癌。这些肿瘤构成了一组功能和生物学特性各异的肿瘤,很少表现出可靠的恶性组织病理学征象。尚无病因学因素被证实与它们相关,其确切的起源和致癌机制仍不清楚。

方法

采用单克隆抗体,结合微波抗原修复和抗生物素蛋白-生物素免疫组织化学方法,对116例原发性胃肠胰神经内分泌肿瘤(GPNTs)进行回顾性研究,检测c-myc、bcl-2、c-erb B-2、c-erb B-3、c-jun和增殖细胞核抗原(PCNA)的表达。作者试图将这种表达与疾病的临床病理结果相关联。

结果

在胰腺神经内分泌肿瘤(PNTs)中,c-myc、bcl-2、c-erb B-2、c-erb B-3和c-jun的免疫反应性分别在100%、45%、24%、7%和24%中检测到。在类癌中,c-myc(63%)、bcl-2(28%)、c-erb B-2(31%)、c-erb B-3(6%)和c-jun(23%)检测到免疫反应性。直肠类癌中c-myc、bcl-2和c-erb B-2免疫反应性的发生率显著高于阑尾类癌,支气管类癌中bcl-2和c-jun免疫反应性的发生率显著高于阑尾类癌。PCNA免疫反应性在恶性PNTs中的发生率显著高于良性PNTs,在空肠和回肠类癌中的发生率也显著高于阑尾类癌。

结论

癌基因c-myc、bcl-2、c-erb B-2和c-jun在人类GPNTs中频繁表达。这些癌基因的表达可能代表了GPNTs发生、恶性转化和进展中的致病事件。通过PCNA对GPNTs细胞动力学进行免疫组织化学评估可能是传统诊断程序的有用辅助手段。

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