PLoS ONE (Jan 2012)

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

  • Luigi Laghi,
  • Stefania Beghelli,
  • Antonino Spinelli,
  • Paolo Bianchi,
  • Gianluca Basso,
  • Giuseppe Di Caro,
  • Anna Brecht,
  • Giuseppe Celesti,
  • Giona Turri,
  • Samantha Bersani,
  • Guido Schumacher,
  • Christoph Röcken,
  • Ilona Gräntzdörffer,
  • Massimo Roncalli,
  • Alessandro Zerbi,
  • Peter Neuhaus,
  • Claudio Bassi,
  • Marco Montorsi,
  • Aldo Scarpa,
  • Alberto Malesci

DOI
https://doi.org/10.1371/journal.pone.0046002
Journal volume & issue
Vol. 7, no. 9
p. e46002

Abstract

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Background and aimsPancreatic 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.MethodsMS-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.ResultsOnly 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.ConclusionsMSI 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.