title: Molecular markers for recurrence and sensitivity to preoperative chemoradiotherapy in locally advanced rectal tumours.
abstract: BACKGROUND
  The objective of our study is to provide predictive markers of locally advanced rectal tumour sensitivity to preoperative chemoradiotherapy in order to identify tumours that present a high risk of recurrence after standard total mesorectal excision surgery and preoperative chemoradiotherapy, according to histological response and microsatellite allelic imbalance (AI).
  
  
  METHODS
  Twenty-nine locally advanced tumours were included in the study and the genomic alterations and the tumour regression grade of paired rectal biopsies (before chemoradiotherapy) and carcinomas (after surgery) were assessed. Clinical and allelotyping data were analysed for local and distant recurrence.
  
  
  RESULTS
  The global AI frequency significantly decreased from 47.4 to 20.3% (p < 0.01) after preoperative treatment. Preoperative chemoradiotherapy significantly induced the loss of cells bearing AI at 8 microsatellites: D18S61, D8S264, D1S305, D10S191, D4S394, D14S65, D17S790 and D10S192. Among these, AI at the D8S264 locus was significantly associated with recurrence in our rectal tumour cohort (p = 0.039).
  
  
  CONCLUSIONS
  Loss of AI at D8S264 is predictive of sensitivity to neoadjuvant treatment; thus, we concluded that the persistence of AI at D8S264 in rectal tumours after preoperative chemoradiotherapy could be considered a molecular marker of recurrence.
authors.affiliation: Service de Chirurgie Générale et Digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Romain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.forename: Cécile
authors.initials: C
authors.lastname: Brigand
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.forename: Anne
authors.initials: A
authors.lastname: Schneider
authors.forename: Dominique
authors.initials: D
authors.lastname: Guenot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D059248:Chemoradiotherapy / Q000379:methods*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016737:Proctocolectomy, Restorative / Q000379:methods; D011379:Prognosis; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor