Deregulated expression of cell cycle-associated proteins in solid pseudopapillary tumor of the pancreas

Solid pseudopapillary tumor of the pancreas was studied in a 20-year-old wo man and a 54-year-old woman. In the younger patient, the tumor had metastas ized to the liver 8 years after distal pancreatectomy, In both neoplasms, t he distinct histologic pattern of solid, pseudopapillary, and degenerative cystic areas was present. Analysis by means of immunohistochemistry reveale d a diffuse expression for vimentin, neuron-specific enolase, and a focal p ositivity for alpha1-antitrypsin, whereas epithelial markers were negative in the tumor of the older patient and only focally expressed in the tumor o f the younger patient. Immunohistochemical analysis of cell cycle-associate d proteins provided an overexpression of cyclin D1 and cyclin D3 in both tu mors, although to varying degrees. In addition, the cyclin-dependent kinase inhibitors p21, and to a lesser extent p27, were up-regulated just as mdm2 . There was no accumulation of p53 protein, and Ki67-positive cells were ex tremely scarce. Analysis of the liver metastases showed an immunoreactive p rofile similar to that of the primary tumor. The results show a deregulatio n of the cell cycle with overexpression of cell cycle activating proteins D 1 and D3 and a probably counterbalancing upregulation of the cyclin-depende nt kinase inhibitors p21 and p27, The findings may explain the low pool of Ki67-reactive tumor cells and the generally good clinical outcome of these tumors. Whether a more profound dysbalance of the cell cycle regulation is responsible for the development of metastatic disease remains to be clarifi ed.