Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma

PLoS One. 2012;7(9):e46002. doi: 10.1371/journal.pone.0046002. Epub 2012 Sep 21.


Background and aims: Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.

Methods: MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.

Results: Only one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.

Conclusions: MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Carcinoma, Pancreatic Ductal / complications*
  • Carcinoma, Pancreatic Ductal / epidemiology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA Mismatch Repair
  • Female
  • Humans
  • Male
  • Methylation
  • Microsatellite Instability*
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Risk Factors


  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MutL Protein Homolog 1

Grant support

This research was funded by the Italian Minister of Health, grant “Tumor stroma interaction, as therapy target in pancreatic cancer” (Ricerca Finalizzata 2005, no. 58). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.