title: [Immunohistochemical and molecular analyis of mismatch repair genes in germ cell tumors].
abstract: Correction of misincorporated nucleotides during DNA replication (mismatch repair) distinguishes histologically similar cancers with distinct biological and clinical behavior. We investigated expression of two mismatch repair genes in testis cancer to determine the expression pattern in histologically distinct subtypes, correlate expression with genetic instability and correlate expression and genetic instability with clinical outcome.
  
  
  METHODS
  118 cases of testis cancer were analyzed. Immunohistochemical analysis of paraffin embedded specimens utilized monoclonal antibody for hMLH1 and hMSH2 mismatch repair proteins. Genetic instability was determined by comparing genomic DNA from microdissected matched normal and tumor cells. PCR amplification of 10 genetic markers assessed loss of heterozygosity and/or microsatellite instability.
  
  
  RESULTS
  hMSH2 staining was associated with pathologic stage (p < 0.001) while hMLH1 staining was associated with cancer specific survival (p = 0.036). Genetic instability was detected in 94% of low hMLH1 and 92% of low hMSH2 staining tumors. Relapse and cancer specific death correlated with genetic instability (p = 0.01 and 0.04 respectively). Overall 9% of tumors exhibited reduced mismatch repair expression, microsatellite instability and an unfavorable clinical outcome.
  
  
  CONCLUSIONS
  Mismatch repair expression and genetic instability define testis cancers with distinct molecular properties and clinical behavior. In conjunction with pathologic examination and serum tumor markers, mismatch repair expression may be an important determinant for clinical management of men with this malignancy.
authors.affiliation: Departamento de Urología, Facultad de Medicina, Pontificia Universidad Católica de Chile. avelasco@med.puc.cl
authors.forename: A
authors.initials: A
authors.lastname: Velasco Palma
authors.forename: E
authors.initials: E
authors.lastname: Riquelme Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Schulze Maroto
authors.forename: L
authors.initials: L
authors.lastname: Villarroel del Pino
authors.forename: F S
authors.initials: FS
authors.lastname: Leach
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology