Nuclear Accumulation of β-Catenin in Well-Differentiated Pancreatic Neuroendocrine Tumors from Patients with Familial Adenomatous Polyposis
Julie C Dueber, Chanjuan Shi. Vanderbilt University Medical Center, Nashville, TN
Background: Although rare, pancreatic neuroendocrine tumors (PanNETs) are the second most common malignancy in the pancreas. Aberrant expression of β-catenin has been described in a number of solid tumors, including solid pseudopapillary tumor of the pancreas. In the current study, we examined the expression of β-catenin in PanNETs.
Design: Two tissue microarrays (TMAs) were constructed using well-differentiated PanNETs from 54 patients who received a Whipple procedure or distal pancreatectomy and/or hepatectomy for primary and metastatic PanNETs during 01/2002-12/2009. Immunohistochemical stains for β-catenin, E-cadherin, chromogranin and synaptophysin were performed on the TMAs. Pathology reports and clinical history were also reviewed.
Results: A genetic syndrome was identified in 11 of 54 (24%) patients, including 6 with multiple endocrine neoplasia type 1, 3 with von Hippel-Lindau disease, and 2 with familial adenomatous polyposis (FAP). Fifteen of them (28%) were functional tumors, including 9 insulinomas, 4 gastrinomas, 1 glucagonoma, and 1 adrenocorticotropic hormone-secreting tumor. The majority of the tumors had moderate to strong membranous β-catenin labeling (48/54, 89%) of which two (4%) also had strong nuclear staining. Of the six that had loss of membranous staining, one showed focal nuclear accumulation. All six cases with loss of membranous staining also displayed loss of E-cadherin expression, whereas all other tumors had intact E-cadherin labeling, including the 2 cases with β-catenin nuclear accumulation. Both patients with FAP had a PanNET showing nuclear accumulation of β-catenin, and liver metastasis was their first presentation. The primary tumor was unresectable for one of the FAP cases, who also had numerous colonic adenomas and multiple colon cancers discovered soon after his diagnosis of PanNET at 61 years of age. The resected liver metastasis showed a well-differentiated neuroendocrine tumor with <2 mitoses/10 HPFs. The second patient was a 44 year old female, who had a known history of FAP and had previously received a total colectomy. The primary was resected which showed a 2 cm well-differentiated PanNETs but with frequent mitoses (focally >20 mitoses/10 HPFs).
Conclusions: Nuclear accumulation of β-catenin can be seen in a small set of PanNETs, which may be related to FAP. PanNETs may be one of the extracolonic presentations in patients with FAP.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 207, Tuesday Morning