Síndrome de Lynch: selección de pacientes para el estudio genético mediante análisis de inestabilidad microsatelital e inmunohistoquímica

• Ana María Wielandt ^[3] ; Alejandro J Zárate ^[3] ; Claudia Hurtado ^[3] ; Paulina Orellana ^[3] ; Karin Álvarez ^[3] ; Eliana Pinto ^[3] ; Luis Contreras ^[1] ; Alejandro Corvalán ^[2] ; Udo Kronberg ^[3] ; Francisco López-Köstner ^[3]
  1. [1] Clínica Las Condes

     Clínica Las Condes

     Santiago, Chile

     
  2. [2] Pontificia Universidad Católica de Chile

     Pontificia Universidad Católica de Chile

     Santiago, Chile

     
  3. [3] Laboratorio de Oncología y Genética Molecular Unidad de Coloproctología

  Mostrar afiliaciones +
• Localización: Revista Médica de Chile, ISSN-e 0034-9887, Vol. 140, Nº. 9, 2012, págs. 1132-1139
• Idioma: español
• Títulos paralelos:
  • Lynch syndrome: selection of families by microsatellite instability and immunohistochemistry
• Enlaces
  • Texto completo
• Resumen

  • Background: Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Im-munohistochemistry (IHC) in the tumor has been proposed. Aim: To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. Material and Methods: From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors. Results: A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. Conclusions: MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes.