title: Low frequency of HNPCC-associated microsatellite instability and aberrant MMR protein expression in early-onset bladder cancer.
abstract: OBJECTIVE
  Recently, it was shown that patients with Lynch syndrome due to an MSH2 mutation are at increased risk for the development of bladder cancer. To further this discussion, we screened the largest investigated cohort of patients with early-onset bladder cancer for microsatellite instability (MSI) and mismatch repair (MMR) deficiency to determine a possible role of Lynch syndrome in young patients with bladder cancer.
  
  
  METHODS
  A total of 109 cases of bladder tumors from young patients (aged <45 years) were examined for MSI (Bethesda consensus panel). Expression of MMR proteins (hMLH1, hMSH2, and hMSH6) was evaluated by immunohistochemistry using a tissue microarray. Results were compared with a series of unselected consecutive bladder tumors (n = 95).
  
  
  RESULTS
  Regarding the frequency of MSI high (1% vs 0%) or abnormal expression of MMR proteins (2% vs 6.5%), no significant difference between the early-onset and unselected patient group was found.
  
  
  CONCLUSIONS
  In young patients with bladder tumors, MSI and defects in MMR protein expression were not more frequent than in a series of consecutive bladder tumors. Most bladder tumors in young patients are not to be attributed to Lynch syndrome.
authors.affiliation: From the Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Giedl
authors.affiliation: Center of Pneumology, Psychosomatic Medicine and Psychotherapy, Clinical Center Donaustauf, Donaustauf, Germany;
authors.forename: Roland
authors.initials: R
authors.lastname: Schneckenpointner
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Filbeck
authors.affiliation: Institute of Pathology and.
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.affiliation: Institute of Pathology and.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.affiliation: St Josef Medical Centre, Department of Urology, University of Regensburg, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: From the Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany;
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: From the Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany; robert.stoehr@uk-erlangen.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins
keywords: Bladder cancer; Early onset; Lynch syndrome; Microsatellite instability