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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere46002
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 21 2012

Fingerprint

pancreatic neoplasms
Epidemiology
Microsatellite Instability
adenocarcinoma
Pancreatic Neoplasms
Microsatellite Repeats
epidemiology
Adenocarcinoma
Hereditary Nonpolyposis Colorectal Neoplasms
microsatellite repeats
neoplasms
Methylation
Repair
Referral and Consultation
Genes
mutation
Sampling
Neoplasms
Defects
DNA Mismatch Repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma. / Laghi, Luigi; Beghelli, Stefania; Spinelli, Antonino; Bianchi, Paolo; Basso, Gianluca; Di Caro, Giuseppe; Brecht, Anna; Celesti, Giuseppe; Turri, Giona; Bersani, Samantha; Schumacher, Guido; Röcken, Christoph; Gräntzdörffer, Ilona; Roncalli, Massimo; Zerbi, Alessandro; Neuhaus, Peter; Bassi, Claudio; Montorsi, Marco; Scarpa, Aldo; Malesci, Alberto.

In: PLoS One, Vol. 7, No. 9, e46002, 21.09.2012.

Research output: Contribution to journalArticle

Laghi, L, Beghelli, S, Spinelli, A, Bianchi, P, Basso, G, Di Caro, G, Brecht, A, Celesti, G, Turri, G, Bersani, S, Schumacher, G, Röcken, C, Gräntzdörffer, I, Roncalli, M, Zerbi, A, Neuhaus, P, Bassi, C, Montorsi, M, Scarpa, A & Malesci, A 2012, 'Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma', PLoS One, vol. 7, no. 9, e46002. https://doi.org/10.1371/journal.pone.0046002
Laghi, Luigi ; Beghelli, Stefania ; Spinelli, Antonino ; Bianchi, Paolo ; Basso, Gianluca ; Di Caro, Giuseppe ; Brecht, Anna ; Celesti, Giuseppe ; Turri, Giona ; Bersani, Samantha ; Schumacher, Guido ; Röcken, Christoph ; Gräntzdörffer, Ilona ; Roncalli, Massimo ; Zerbi, Alessandro ; Neuhaus, Peter ; Bassi, Claudio ; Montorsi, Marco ; Scarpa, Aldo ; Malesci, Alberto. / Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma. In: PLoS One. 2012 ; Vol. 7, No. 9.
@article{c327d7b7991b4333af3a4f9256b7c657,
title = "Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma",
abstract = "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.",
author = "Luigi Laghi and Stefania Beghelli and Antonino Spinelli and Paolo Bianchi and Gianluca Basso and {Di Caro}, Giuseppe and Anna Brecht and Giuseppe Celesti and Giona Turri and Samantha Bersani and Guido Schumacher and Christoph R{\"o}cken and Ilona Gr{\"a}ntzd{\"o}rffer and Massimo Roncalli and Alessandro Zerbi and Peter Neuhaus and Claudio Bassi and Marco Montorsi and Aldo Scarpa and Alberto Malesci",
year = "2012",
month = "9",
day = "21",
doi = "10.1371/journal.pone.0046002",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma

AU - Laghi, Luigi

AU - Beghelli, Stefania

AU - Spinelli, Antonino

AU - Bianchi, Paolo

AU - Basso, Gianluca

AU - Di Caro, Giuseppe

AU - Brecht, Anna

AU - Celesti, Giuseppe

AU - Turri, Giona

AU - Bersani, Samantha

AU - Schumacher, Guido

AU - Röcken, Christoph

AU - Gräntzdörffer, Ilona

AU - Roncalli, Massimo

AU - Zerbi, Alessandro

AU - Neuhaus, Peter

AU - Bassi, Claudio

AU - Montorsi, Marco

AU - Scarpa, Aldo

AU - Malesci, Alberto

PY - 2012/9/21

Y1 - 2012/9/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84866662081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866662081&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0046002

DO - 10.1371/journal.pone.0046002

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e46002

ER -