6 research outputs found
Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma
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