title: [Should we systematically screen for Lynch syndrome in patients with upper urinary tract carcinoma?].
abstract: OBJECTIVE
  The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening.
  
  
  METHODS
  Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center. Clinicopathological characteristics and survival data of patients were collected (median follow-up = 42.5 months). Immunohistochemistry was performed by tissue microarray (TMA), in order to detect mutations in mismatch repair genes. Results obtained after TMA analysis were confirmed at a molecular level by microsatellite instability (MSI) analysis.
  
  
  RESULTS
  Mutations in mismatch repair genes were detected in seven patients (4.8%) at immunohistochemistry screening, and confirmed by MSI analysis for five of them (3.4%). Clinicopathological characteristics and survival data did not differ significantly in patients with instability compared with patients without. After a median follow-up of 42.5 months, none of them experienced a new HNPCC manifestation.
  
  
  CONCLUSIONS
  The frequency of mutations in mismatch repair genes in UUT-TCC was very low, with a good accuracy of immunohistochemistry. Systematic screening should not be proposed in daily practice.
authors.affiliation: Hôpital Cochin, AP-HP, service d'urologie, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors.forename: Giscard S
authors.initials: GS
authors.lastname: Olagui
authors.affiliation: Hôpital Cochin, AP-HP, service d'urologie, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France, Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Pignot
authors.affiliation: Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France, Hôpital Cochin, AP-HP, service d'anatomopathologie, 75014 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Rouquette
authors.affiliation: Hôpital Cochin, AP-HP, service d'anatomopathologie, 75014 Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Vieillefond
authors.affiliation: Hôpital Cochin, AP-HP, service d'urologie, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Amsellem-Ouazana
authors.affiliation: Hôpital Cochin, AP-HP, service d'urologie, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France, Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France.
authors.forename: Nicolas Barry
authors.initials: NB
authors.lastname: de Longchamps
authors.affiliation: Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France, Hôpital Cochin, AP-HP, service d'anatomopathologie, 75014 Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Radenen
authors.affiliation: Hôpital Cochin, AP-HP, service d'urologie, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France, Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Zerbib
authors.affiliation: Université Paris-Descartes, Sorbonne-Paris-Cité, faculté de sciences et de médecine, 75014 Paris, France, Hôpital Cochin, AP-HP, service d'anatomopathologie, 75014 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014516:Ureteral Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C516892:BAT26 microsatellite DNA; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D005819:Genetic Markers; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: Lynch syndrome; immunochemistry; microsatellite instability; upper urinary tract carcinoma
vernacular_title: Tumeurs du haut appareil urinaire et syndrome de Lynch : doit-on proposer un dépistage systématique ?