Familial Cancer

, Volume 11, Issue 4, pp 571–578

Bethesda criteria for microsatellite instability testing: impact on the detection of new cases of Lynch syndrome

Authors

    • Serviço de GastrenterologiaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Pedro Lage
    • Serviço de GastrenterologiaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
    • Clínica de Risco FamiliarInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Sara Belga
    • Serviço de GastrenterologiaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Bruno Filipe
    • Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Inês Francisco
    • Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Paula Rodrigues
    • Clínica de Risco FamiliarInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Ricardo Fonseca
    • Departamento de Patologia MorfológicaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Paula Chaves
    • Departamento de Patologia MorfológicaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Isabel Claro
    • Serviço de GastrenterologiaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
    • Clínica de Risco FamiliarInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • Cristina Albuquerque
    • Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
  • António Dias Pereira
    • Serviço de GastrenterologiaInstituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Original Article

DOI: 10.1007/s10689-012-9550-6

Cite this article as:
Serrano, M., Lage, P., Belga, S. et al. Familial Cancer (2012) 11: 571. doi:10.1007/s10689-012-9550-6

Abstract

In 1997 Bethesda Guidelines (BG) were established and in 2004 those criteria were revised (RBG), with the main goal of selecting colorectal cancers (CRC) that should be subjected to microsatellite instability (MSI) testing. High microsatellite instability (MSI-H) is an intermediate marker for mutational analysis of the mismatch repair (MMR) genes involved in the genesis of Lynch Syndrome (LS). We aimed to evaluate and compare BG/RBG in the detection of MSI-H and subsequent identification of pathogenic MMR genes mutations. We included 174 patients with CRC and indication for MSI analysis according to BG or RBG. MSI testing was performed with the Bethesda markers and mutational analysis of MLH1, MSH2 and MSH6 genes undertaken with DGGE, MLPA and direct sequencing. One hundred fourteen of 174 patients (65.5 %) fulfilled BG and all of them RBG. With the BG, MSI-H was detected in 37/114 (32.5 %) CRCs and mutational analysis was positive in 14/37 (37.8 %) patients. The RBG led to detection of MSI-H in 49/174 (28.2 %) of the CRCs, having the mutational analysis been positive in 16/49 (32.7 %) patients. We could identify 14/114 (12.3 %) new cases of LS, through BG and 16/174 (9.2 %) via RBG. BG presented a similar overall percentage for the detection of MSI-H and mutations when compared with RBG. RBG implicated the analysis of more patients, though they gave rise to detection of two additional LS cases. This difference has a significant impact on the establishment of preventive measures, mainly for CRC, in all the mutation-carriers belonging to these families.

Keywords

Lynch syndromeBethesda guidelinesRevised Bethesda guidelinesMicrosatellite instability

Copyright information

© Springer Science+Business Media B.V. 2012