Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas

Solid pseudopapillary tumor of pancreas (SPT) is a rare neoplasm that occurs most often in young females with the two distinct features, the 'solid-cystic' gross appearance, and the 'solid-pseudopapillary' microscopic pattern. It has been reported that almost all SPT tumors contain a mutation in the β-catenin gene; however, the histogenetic origin of this tumor remains largely a mystery. E-cadherin is a cell adhesion molecule that links to catenins to form cell adhesion junctions, which is associated with the cytoskeleton formation. In this study, we examined the expression of E-cadherin and β-catenin from SPT in an attempt to determine the molecular basis for the unusual morphology of this tumor. Nine cases of SPT were retrieved from Surgical Pathologic Archives of three institutions, including one male and eight females. H&E slides of each case were reviewed to confirm the diagnosis. The β-catenin gene was sequenced in one case. E-cadherin and β-catenin immunostains, were performed on all nine cases. Sequencing analysis on one case showed a point mutation of the β-catenin gene, confirming previous findings that almost all SPT tumors contain mutation in the β-catenin gene. Immunostains showed that, in both solid and pseudopapillary areas, all the tumor cells lost expression of E-cadherin, and β-catenin nuclear expression was observed in all cases. Our findings suggest that loss of cytoplasmic β-catenin protein in the cell adhesion complex due to β-catenin gene mutation, results in instability of the complex, loss of E-cadherin in cell membrane, and eventually dissociation of the tumor cells to form the pseudopapillary pattern.