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 woman and a 54-year-old woman. In the younger patient, the tumor had metastasized to the liver 8 years after distal pancreatectomy. In both neoplasms, the distinct histologic pattern of solid, pseudopapillary, and degenerative cystic areas was present. Analysis by means of immunohistochemistry revealed a diffuse expression for vimentin, neuron-specific enolase, and a focal positivity for al-antitrypsin, whereas epithelial markers were negative in the tumor of the older patient and only focally expressed in the tumor of the younger patient. Immunohistochemical analysis of cell cycle-associated proteins provided an overexpression of cyclin D1 and cyclin D3 in both tumors, 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 extremely scarce. Analysis of the liver metastases showed an immunoreactive profile similar to that of the primary tumor. The results show a deregulation of the cell cycle with overexpression of cell cycle-activating proteins D1 and D3 and a probably counterbalancing upregulation of the cyclin-dependent 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 clarified.
Institute of Pathology, University of Munich, Germany.
J
J
Müller-Höcker
C H
CH
Zietz
A
A
Sendelhofert
D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002648:Child; D019938:Cyclin D1 / Q000378:metabolism*; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; C493956:CDKN1A protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases