Clinical and molecular detection of inherited colorectal cancers in northeast Italy: A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy

E. Urso, M. Agostini, S. Pucciarelli, M. Rugge, R. Bertorelle, I. Maretto, C. Bedin, E. D'Angelo, C. Mescoli, M. Zorzi, A. Viel, G. Bruttocao, B. Ferraro, F. Erroi, P. Contin, G. L. De Salvo, D. Nitti

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. TheMSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

Original languageEnglish
Pages (from-to)857-864
Number of pages8
JournalTumor Biology
Volume33
Issue number3
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Italy
Colorectal Neoplasms
Prospective Studies
Mutation
Incidence
Methylation
Adenomatous Polyposis Coli
Germ-Line Mutation
Immunohistochemistry
Phenotype

Keywords

  • Genetics screening
  • Incidence of familial CRCs
  • Lynch syndrome

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Clinical and molecular detection of inherited colorectal cancers in northeast Italy : A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy. / Urso, E.; Agostini, M.; Pucciarelli, S.; Rugge, M.; Bertorelle, R.; Maretto, I.; Bedin, C.; D'Angelo, E.; Mescoli, C.; Zorzi, M.; Viel, A.; Bruttocao, G.; Ferraro, B.; Erroi, F.; Contin, P.; De Salvo, G. L.; Nitti, D.

In: Tumor Biology, Vol. 33, No. 3, 06.2012, p. 857-864.

Research output: Contribution to journalArticle

Urso, E, Agostini, M, Pucciarelli, S, Rugge, M, Bertorelle, R, Maretto, I, Bedin, C, D'Angelo, E, Mescoli, C, Zorzi, M, Viel, A, Bruttocao, G, Ferraro, B, Erroi, F, Contin, P, De Salvo, GL & Nitti, D 2012, 'Clinical and molecular detection of inherited colorectal cancers in northeast Italy: A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy', Tumor Biology, vol. 33, no. 3, pp. 857-864. https://doi.org/10.1007/s13277-011-0312-0
Urso, E. ; Agostini, M. ; Pucciarelli, S. ; Rugge, M. ; Bertorelle, R. ; Maretto, I. ; Bedin, C. ; D'Angelo, E. ; Mescoli, C. ; Zorzi, M. ; Viel, A. ; Bruttocao, G. ; Ferraro, B. ; Erroi, F. ; Contin, P. ; De Salvo, G. L. ; Nitti, D. / Clinical and molecular detection of inherited colorectal cancers in northeast Italy : A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy. In: Tumor Biology. 2012 ; Vol. 33, No. 3. pp. 857-864.
@article{4b60a6ce874c40afa8ac2dc42fcb1da3,
title = "Clinical and molecular detection of inherited colorectal cancers in northeast Italy: A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy",
abstract = "The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4{\%}) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. TheMSI test was performed on 393 tumours, and 46 (12{\%}) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70{\%}) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4{\%} of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3{\%} and of MSI-H phenotype was 12{\%}. MLH1 methylation and BRAF mutation can exclude 70{\%} of MSI-H cases from gene sequencing.",
keywords = "Genetics screening, Incidence of familial CRCs, Lynch syndrome",
author = "E. Urso and M. Agostini and S. Pucciarelli and M. Rugge and R. Bertorelle and I. Maretto and C. Bedin and E. D'Angelo and C. Mescoli and M. Zorzi and A. Viel and G. Bruttocao and B. Ferraro and F. Erroi and P. Contin and {De Salvo}, {G. L.} and D. Nitti",
year = "2012",
month = "6",
doi = "10.1007/s13277-011-0312-0",
language = "English",
volume = "33",
pages = "857--864",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Clinical and molecular detection of inherited colorectal cancers in northeast Italy

T2 - A first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy

AU - Urso, E.

AU - Agostini, M.

AU - Pucciarelli, S.

AU - Rugge, M.

AU - Bertorelle, R.

AU - Maretto, I.

AU - Bedin, C.

AU - D'Angelo, E.

AU - Mescoli, C.

AU - Zorzi, M.

AU - Viel, A.

AU - Bruttocao, G.

AU - Ferraro, B.

AU - Erroi, F.

AU - Contin, P.

AU - De Salvo, G. L.

AU - Nitti, D.

PY - 2012/6

Y1 - 2012/6

N2 - The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. TheMSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

AB - The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. TheMSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

KW - Genetics screening

KW - Incidence of familial CRCs

KW - Lynch syndrome

UR - http://www.scopus.com/inward/record.url?scp=84863589779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863589779&partnerID=8YFLogxK

U2 - 10.1007/s13277-011-0312-0

DO - 10.1007/s13277-011-0312-0

M3 - Article

C2 - 22278153

AN - SCOPUS:84863589779

VL - 33

SP - 857

EP - 864

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 3

ER -