Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2016; 8(8): 615-622
Published online Aug 15, 2016. doi: 10.4251/wjgo.v8.i8.615
Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms
Vivian Weiss, Julie Dueber, Jesse P Wright, Justin Cates, Frank Revetta, Alexander A Parikh, Nipun B Merchant, Chanjuan Shi
Vivian Weiss, Julie Dueber, Justin Cates, Frank Revetta, Chanjuan Shi, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Jesse P Wright, Alexander A Parikh, Department of Surgery, Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Nipun B Merchant, Department of Surgery, Surgical Oncology, University of Miami Hospital, Miami, FL 33165, United States
Author contributions: Weiss V and Dueber J collected the pathologic data and wrote the manuscript; Wright JP analyzed Ki67 and collected the clinical data; Cates J performed statistical analysis and edited the manuscript; Revetta F performed immunohistochemistry; Parikh AA, Merchant NB and Shi C designed the study and edited the manuscript.
Institutional review board statement: The study was reviewed and approved by the Vanderbilt Institutional Review Board.
Institutional animal care and use committee statement: Not applicable.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Technical appendix is available from the corresponding author at chanjuan.shi@vanderbilt.edu. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chanjuan Shi, MD, PhD, Associate Professor, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Medical Center North C-2310D, 1121 21st Ave. S, Nashville, TN 37232, United States. chanjuan.shi@vanderbilt.edu
Telephone: +1-615-9368342 Fax: +1-615-3437023
Received: March 28, 2016
Peer-review started: March 28, 2016
First decision: May 16, 2016
Revised: May 24, 2016
Accepted: June 1, 2016
Article in press: June 3, 2016
Published online: August 15, 2016
Abstract

AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms (PanNENs).

METHODS: Tissue microarrays containing 88 PanNENs 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 PanNENs as compared to 47% (35/74) of stage I/II tumors (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 PanNENs as compared to 0% (0/74) of stage I/II tumors (P = 0.02). The case with metastasectomy also only 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 PanNENs, but did not Impact DSS. PanNENs in FAP patients demonstrated nuclear β-catenin accumulation and loss of APC.

Keywords: β-catenin, Familial adenomatous polyposis, Pancreatic neuroendocrine neoplasm, Adenomatous polyposis coli, E-cadherin

Core tip: Dysregulation of the Wnt/β-catenin pathway is present in some pancreatic neuroendocrine neoplasms (PanNENs). However, compared to other malignancies, this signaling pathway may have different functions in PanNENs as strong membranous β-catenin expression is more frequently present in stage III/IV tumors and membranous expression of β-catenin and E-cadherin does not have a prognostic importance in this setting. Additionally, PanNENs arising in patients with familial adenomatous polyposis (FAP) demonstrate abnormal nuclear β-catenin accumulation, and PanNENs may be one of the extraintestinal manifestations of FAP.