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