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

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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.

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Acknowledgments

The authors thank Isadora Rosa, MD, for her helpful comments on the manuscript and statistical advice.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Professor Lima Basto, 1099-023, Lisbon, Portugal

    Miguel Serrano, Pedro Lage, Sara Belga, Isabel Claro & António Dias Pereira

  2. Clínica de Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal

    Pedro Lage, Paula Rodrigues & Isabel Claro

  3. Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal

    Bruno Filipe, Inês Francisco & Cristina Albuquerque

  4. Departamento de Patologia Morfológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal

    Ricardo Fonseca & Paula Chaves

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  1. Miguel Serrano
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Correspondence to Miguel Serrano.

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Serrano, M., Lage, P., Belga, S. et al. Bethesda criteria for microsatellite instability testing: impact on the detection of new cases of Lynch syndrome. Familial Cancer 11, 571–578 (2012). https://doi.org/10.1007/s10689-012-9550-6

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  • DOI: https://doi.org/10.1007/s10689-012-9550-6

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