title: Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Vivian
authors: V
authors: Weiss
authors: 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.
authors: Julie
authors: J
authors: Dueber
authors: 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.
authors: Jesse P
authors: JP
authors: Wright
authors: 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.
authors: Justin
authors: J
authors: Cates
authors: 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.
authors: Frank
authors: F
authors: Revetta
authors: 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.
authors: Alexander A
authors: AA
authors: Parikh
authors: 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.
authors: Nipun B
authors: NB
authors: Merchant
authors: 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.
authors: Chanjuan
authors: C
authors: Shi
keywords: Adenomatous polyposis coli; E-cadherin; Familial adenomatous polyposis; Pancreatic neuroendocrine neoplasm; β-catenin