Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary mucinous carcinomas are usually microsatellite stable.
Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level. The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1-) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.
Lüttges
Jutta
J
Department of Pathology, University of Kiel, Germany. jluettges@path.uni-kiel.de
Beyser
Kurt
K
Pust
Susanne
S
Paulus
Anja
A
Rüschoff
Josef
J
Klöppel
Günter
G
D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins; D002648:Child; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D042282:Microdissection; D018895:Microsatellite Repeats; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein