Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms

• 作者: Vivian Weiss Julie Dueber Jesse P Wright Justin Cates Frank Revetta Alexander A Parikh Nipun B Merchant Chanjuan Shi
• 来源期刊: 世界胃肠肿瘤学杂志：英文版（电子版）
• 学科: 医学
• 关键词: β-catenin FAMILIAL adenomatous POLYPOSIS PANCREATIC NEUROENDOCRINE NEOPLASM Adenomatous POLYPOSIS COLI E-cadherin
• 年，卷（期）: 2016,（8）
• 页码范围: 615-622
• 页数: 8页
• 分类号: R735.9

摘要

AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms(PanN ENs). METHODS: Tissue microarrays containing 88 PanN ENs were immunohistochemically labeled with antibodies to β-catenin, E-cadherin, adenomatous polyposis coli(APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others(n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed. Patients’ demographics, clinicopathologic features, and immunohistochemical results from 87 primary tumors were compared between patients with low stage(stage Ⅰ/Ⅱ) and high stage(stage Ⅲ/Ⅳ) tumors. In addition, correlation of immunohistochemical results from primary tumors with disease-specific survival(DSS) was evaluated. RESULTS: Strong membranous β-catenin staining in the primary tumor was observed in all 13 stage Ⅲ/Ⅳ Pan NENs as compared to 47%(35/74) of stage Ⅰ/Ⅱtumors(P < 0.01). However, the strong membranous β-catenin staining was unassociated with tumor grade or DSS. Decreased membranous β-catenin staining was associated with decreased membranous E-cadherin labeling. Nuclear β-catenin staining was seen in 15%(2/13) of stage Ⅲ/Ⅳ Pan NENs as compared to 0%(0/74) of stage Ⅰ/Ⅱ tumors(P = 0.02). The case with metastasectomy only also showed nuclear β-catenin staining. Two of the three cases with nuclear β-catenin staining were familial adenomatous polyposis(FAP) patients. Lack of APC expression was seen in 70%(57/81) of the cases, including the 3 cases with nuclear β-catenin staining. Expression of E-cadherin and APC in primary tumor was not correlated with tumor grade, tumor stage, or disease specific survival. CONCLUSION: The Wnt/β-catenin pathway was altered in some PanN ENs, but did not Impact DSS. PanN ENs in FAP patients demonstrated nuclear β-catenin accumulation and loss of APC.