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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

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Tumor Biology

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 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. The MSI 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.

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Acknowledgments

We are grateful to Associazione Italiana Ricerca sul Cancro (AIRC) e Banca Antonveneta Foundation for their financial support. Biological samples were provided by 2nd Surgical Clinic, Tumor Tissue Biobank.

Conflicts of interest

None

Author information

Author notes

  1. P. Contin

    Present address: Surgical Department, Heidelberg University, Heidelberg, Germany

Authors and Affiliations

  1. Clinica Chirurgica 2nd, Dipartimento Scienze Chirurgiche, Oncologiche e Gastroenterologiche, University of Padova, Padua, Italy, Policlinico, VI piano, Via Giustiniani, 2, 35128, Padua, Italy

    E. Urso, M. Agostini, S. Pucciarelli, I. Maretto, C. Bedin, P. Contin & D. Nitti

  2. Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA

    M. Agostini

  3. Istituto Ricerca Pediatrica, Città della Speranza, Padua, Italy

    M. Agostini, C. Bedin & E. D’Angelo

  4. Servizio di Anatomia Patologica, University of Padova, Padua, Italy

    M. Rugge & C. Mescoli

  5. Immunologia e Diagnostica Molecolare Oncologica, IOV-IRCCS, Padua, Italy

    R. Bertorelle

  6. Registro Tumori del Veneto, IOV-IRCCS, Padua, Italy

    M. Zorzi

  7. Centro Riferimento Oncologico, IRCCS, CRO, Aviano, Italy

    A. Viel

  8. Chirurgia Geriatrica, University of Padova, Padua, Italy

    G. Bruttocao

  9. Chirurgia Generale, Ospedale San Antonio, ULSS 16, Padua, Italy

    B. Ferraro

  10. Clinica Chirurgica 3, University of Padova, Padua, Italy

    F. Erroi

  11. Servizio di Epidemiologia Clinica, IOV-IRCCS, Padua, Italy

    G. L. De Salvo

  12. Clinica Chirurgica 2nd, University of Padova, Padova, Italy

    E. D’Angelo

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  1. E. Urso
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  16. G. L. De Salvo
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Correspondence to E. Urso.

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Synopsis

For evaluate prospectively the incidence of hereditary colorectal cancers (CRC) in a region of Italy, 430 patients were enrolled. A strong family history of CRC was present in 4% of cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3%.

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Urso, E., Agostini, M., Pucciarelli, S. et al. Clinical and molecular detection of inherited colorectal cancers in northeast Italy. Tumor Biol. 33, 857–864 (2012). https://doi.org/10.1007/s13277-011-0312-0

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  • DOI: https://doi.org/10.1007/s13277-011-0312-0

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