title: Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients.
abstract: OBJECTIVE
  About 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients.
  
  
  METHODS
  Mismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres.
  
  
  RESULTS
  231 patients (median age: 81, range: 75-100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05-6.44; p=0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%).
  
  
  CONCLUSIONS
  deficient DNA mismatch repair phenotype is a prognostic factor in stage II colorectal tumour in elderly patients. Our results suggest that mismatch repair phenotype should be taken in consideration for adjuvant chemotherapy decision in elderly patients.
authors.affiliation: Gastroenterology, Avicenne Hospital, APHP, Université Paris 13, Bobigny, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Aparicio
authors.forename: Olivier
authors.initials: O
authors.lastname: Schischmanoff
authors.forename: Cecile
authors.initials: C
authors.lastname: Poupardin
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.forename: Celine
authors.initials: C
authors.lastname: Angelakov
authors.forename: Christophe
authors.initials: C
authors.lastname: Barrat
authors.forename: Vincent
authors.initials: V
authors.lastname: Levy
authors.forename: Laurence
authors.initials: L
authors.lastname: Choudat
authors.forename: Joel
authors.initials: J
authors.lastname: Cucherousset
authors.forename: Marouane
authors.initials: M
authors.lastname: Boubaya
authors.forename: Christine
authors.initials: C
authors.lastname: Lagorce
authors.forename: Gaetan Des
authors.initials: GD
authors.lastname: Guetz
authors.forename: Philippe
authors.initials: P
authors.lastname: Wind
authors.forename: Robert
authors.initials: R
authors.lastname: Benamouzig
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics / Q000502:physiology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies