title: DNA Methylation profiles as predictors of recurrence in non muscle invasive bladder cancer: an MS-MLPA approach.
abstract: BACKGROUND
  Although non muscle invasive bladder cancer (NMIBC) generally has a good long-term prognosis, up to 80% of patients will nevertheless experience local recurrence after the primary tumor resection. The search for markers capable of accurately identifying patients at high risk of recurrence is ongoing. We retrospectively evaluated the methylation status of a panel of 24 tumor suppressor genes (TIMP3, APC, CDKN2A, MLH1, ATM, RARB, CDKN2B, HIC1, CHFR, BRCA1, CASP8, CDKN1B, PTEN, BRCA2, CD44, RASSF1, DAPK1, FHIT, VHL, ESR1, TP73, IGSF4, GSTP1 and CDH13) in primary lesions to obtain information about their role in predicting local recurrence in NMIBC.
  
  
  METHODS
  Formaldehyde-fixed paraffin-embedded (FFPE) samples from 74 patients operated on for bladder cancer were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): 36 patients had relapsed and 38 were disease-free at the 5-year follow up. Methylation status was considered as a dichotomous variable and genes showing methylation ≥20% were defined as "positive".
  
  
  RESULTS
  Methylation frequencies were higher in non recurring than recurring tumors. A statistically significant difference was observed for HIC1 (P = 0.03), GSTP1 (P = 0.02) and RASSF1 (P = 0.03). The combination of the three genes showed 78% sensitivity and 66% specificity in identifying recurrent patients, with an overall accuracy of 72%.
  
  
  CONCLUSIONS
  Our preliminary data suggest a potential role of HIC1, GSTP1 and RASSF1 in predicting local recurrence in NMIBC. Such information could help clinicians to identify patients at high risk of recurrence who require close monitoring during follow up.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P, Maroncelli 40, Meldola 47014, Italy. w.zoli@irst.emr.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Casadio
authors.forename: Chiara
authors.initials: C
authors.lastname: Molinari
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
authors.forename: Michela
authors.initials: M
authors.lastname: Tebaldi
authors.forename: Roberta
authors.initials: R
authors.lastname: Gunelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Serra
authors.forename: Fabio
authors.initials: F
authors.lastname: Falcini
authors.forename: Chiara
authors.initials: C
authors.lastname: Zingaretti
authors.forename: Rosella
authors.initials: R
authors.lastname: Silvestrini
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
mesh_terms: D000368:Aged; D015331:Cohort Studies; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology