Expression of novel markers of pancreatic ductal adenocarcinoma in pancreatic nonductal neoplasms: additional evidence of different genetic pathways

• Published in: Modern pathology 2005-06, Vol.18 (6), p.752-761
• Main Authors: Cao, Dengfeng, Maitra, Anirban, Saavedra, Jorge-Albores, Klimstra, David S, Adsay, N Volkan, Hruban, Ralph H
• Format: Article
• Language: English
• Subjects: 14-3-3 Proteins; acinar cell carcinoma; Antigens, Neoplasm; beta Catenin; Biomarkers, Tumor - analysis; Carcinoma, Acinar Cell - metabolism; Carcinoma, Acinar Cell - pathology; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Carrier Proteins - analysis; Cytoskeletal Proteins - analysis; DNA-Binding Proteins - analysis; Exonucleases - analysis; Exoribonucleases; Fibronectins - analysis; gamma-Synuclein; GPI-Linked Proteins; Heat-Shock Proteins - analysis; HSP47 Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins - analysis; Laboratory Medicine; Medicine; Medicine & Public Health; Membrane Glycoproteins - analysis; Mesothelin; Microfilament Proteins - analysis; Neoplasm Proteins - analysis; Nerve Tissue Proteins - analysis; novel markers; original-article; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; pancreatoblastoma; Pathology; Serpins - analysis; Smad4 Protein; solid pseudopapillary tumor; Synucleins; tissue microarray; Trans-Activators - analysis; undifferentiated carcinoma with osteoclastic-like giant cells
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800363

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 (