Solid pseudopapillary
tumor,
pancreatoblastoma,
undifferentiated carcinoma with osteoclastic-like giant cells, and
acinar cell carcinomas are rare pancreatic nonductal
neoplasms. Compared to the significant advances in our understanding of the pathogenesis of pancreatic ductal
adenocarcinomas in the last decades, the molecular mechanisms underlying pancreatic nonductal
neoplasms are poorly understood. In order to elucidate their molecular pathogenesis, we constructed tissue microarrays to study the expression of some novel pancreatic ductal
adenocarcinoma-associated
tumor markers in these nonductal
pancreatic neoplasms. We analyzed nine markers including tumor suppressor gene (14-3-3 sigma), proliferation marker (
topoisomerase II alpha), epithelial markers (prostate stem cell
antigen,
mesothelin and
cytokeratin 19), stromal markers (
fascin, hsp47 and
fibronectin), and
gamma-synuclein whose function is not delineated. In addition, we included tumor suppressor gene DPC4 and oncogene
Beta-catenin to further confirm their expression in pancreatic nonductal
tumors. Our results showed that in contrast to pancreatic ductal
adenocarcinomas that show loss of Dpc4
protein in 55% of cases, loss of Dpc4 expression is absent in pancreatic nonductal
neoplasms. Expression of 14-3-3 sigma is frequently seen in both pancreatic nonductal
neoplasms (25-100%) and ductal
adenocarcinomas (89%). Aberrant nuclear expression of
beta-catenin is common in pancreatic nonductal
neoplasms, specifically in solid pseudopapillary
tumors (88%) and pancreatoblastomas (100%) but is rarely seen in pancreatic ductal
adenocarcinomas (<5%). Expression of
topoisomerase II alpha is not seen in solid pseudopapillary
tumors and
undifferentiated carcinomas with osteoclastic-like giant cells but is focally seen in pancreatoblastomas (50%) and
acinar cell carcinomas (85%). Expression of PSCA and
mesothelin was observed in pancreatic nonductal
neoplasms but their expression was seen less frequently (0-50%) and weaker than that in pancreatic ductal
adenocarcinomas (60-100%). CK19, a marker of pancreatic ductal
adenocarcinomas, is not expressed in pancreatic nonductal
neoplasms. Expression of
gamma-synuclein as well as stromal markers (
fascin, hsp47 and
fibronectin) is frequently seen in both. Our findings indicate pancreatic nonductal
neoplasms have distinctive patterns of
protein expression relative to pancreatic ductal
adenocarcinomas and suggest that pancreatic nonductal
neoplasms have different genetic pathways from the more common pancreatic ductal
adenocarcinomas.