Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

Abstract

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.

Correlation between patterns of DNA mismatch repair hmlh1 and hmsh2 protein expression and progression of dysplasia in intraductal papillary mucinous neoplasms of the pancreas

“…We show here that in this group of IPMNs associated with pancreatic adenocarcinoma, defective DNA mismatch repair due to inactivation of hMLH1 or hMSH2 genes is not involved. Our results confirm a series composed of IPMNs of various types (low-grade dysplasia, high-grade dysplasia, carcinoma) recently reported by Luttges et al [12]. As MSI has been mainly observed in tumours within the spectrum of the HNPCC and Muir-Torre syndromes, it is not surprising that this phenomenon is not present in IPMNs, a type of tumour that has not been described in patients with these syndromes.…”

Colloid (mucinous non-cystic) carcinoma of the pancreas: A case report

“…The pancreatic carcinomas with mucinous phenotype (MUC2 + /MUC1 -) usually do not exhibit mutations in the mismatch repair genes and are microsatellite stable. This indicates why the malignancy of CC and IPMN is weaker than that of PDAC (1,14).…”

Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct—an immunohistochemical study of 110 cases of hepatolithiasis

“…IPMN-P is classified histopathologically into three types [21][22][23][24][25][26]; MUC1K/MUC2C type characterized by dark columnar cells, MUC1K/MUC2K type characterized by clear cells containing abundant intracytoplasmic mucin, and MUC1C/MUC2G type characterized by papillary proliferation of compact or oncocytic tumor cells. Interestingly, the IPN-B cases in this study could be classified into similar groups based on the MUC1/MUC2 immunophenotypes.…”