Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Gastroenterology. 2018 Mar;154(4):1061-1065. doi: 10.1053/j.gastro.2017.11.009. Epub 2017 Nov 20.

Abstract

Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

Keywords: Cytokine Production; Marker; Pancreatic Cancer; T-cell Activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Pancreatic Ductal / chemistry
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology
  • DNA-Binding Proteins / analysis
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / analysis
  • MutL Protein Homolog 1 / analysis
  • MutS Homolog 2 Protein / analysis
  • Neoplasms, Cystic, Mucinous, and Serous / chemistry
  • Neoplasms, Cystic, Mucinous, and Serous / genetics*
  • Neoplasms, Cystic, Mucinous, and Serous / immunology
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Time Factors

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein