Tumor-suppressing pathways in cystic pancreatic tumors.
OBJECTIVE
Serous and mucinous cystic pancreatic tumors have different clinical behavior. We evaluated whether they also have genotypic differences by analyses of the tumor suppressor genes, p16INK4a, p53, and DPC4.


METHODS
Seven serous cystadenomas (SCA) and seven malignant mucinous cystadenocarcinomas (MCC) were analyzed for alterations in the tumor suppressor genes p16INK4a, p53, and DPC4 by single-strand conformational variant analysis, direct sequencing, and immunohistochemical analysis. Methylation-specific polymerase chain reaction analysis was performed to identify p16INK4a promoter hypermethylation. Clinical data were compared with genetic data.


RESULTS
None of the seven patients with SCAs but five of the seven patients with MCCs died of the tumor after a median follow-up of 44.5 months (range, 4-169 months). All seven MCCs had alterations in at least one tumor suppressor gene compared with none of the seven SCAs. Of the seven MCCs, three had inactivating p16INK4a promoter hypermethylation, five had p53 alterations, and three had DPC4 mutations.


CONCLUSIONS
The tumor suppressor genes p16INK4a, p53, and appear to play an important role in the tumorigenesis of MCCs but not SCAs. These molecular data underscore the clinical and histologic differences of serous and mucinous cystic pancreatic tumors.
Gerdes
Berthold
B
Department of General Surgery, Philipps University of Marburg, Germany.
Wild
Anja
A
Wittenberg
Judith
J
Barth
Peter
P
Ramaswamy
Annette
A
Kersting
Michael
M
Lüttges
Jutta
J
Klöppel
Günter
G
Bartsch
Detlef K
DK
D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018282:Cystadenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53