title: Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. luigi.laghi@humanitas.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Laghi
authors.forename: Stefania
authors.initials: S
authors.lastname: Beghelli
authors.forename: Antonino
authors.initials: A
authors.lastname: Spinelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianchi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Basso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Caro
authors.forename: Anna
authors.initials: A
authors.lastname: Brecht
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celesti
authors.forename: Giona
authors.initials: G
authors.lastname: Turri
authors.forename: Samantha
authors.initials: S
authors.lastname: Bersani
authors.forename: Guido
authors.initials: G
authors.lastname: Schumacher
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Ilona
authors.initials: I
authors.lastname: Gräntzdörffer
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbi
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassi
authors.forename: Marco
authors.initials: M
authors.lastname: Montorsi
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Alberto
authors.initials: A
authors.lastname: Malesci
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1