title: Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer.
abstract: BACKGROUND
  Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer.
  
  
  METHODS
  Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers.
  
  
  RESULTS
  Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P = 0.015).
  
  
  CONCLUSIONS
  Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.
authors.affiliation: Department of Surgery, Princess Alexandra Hospital, Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Research Foundation Clinical Research Centre, Brisbane, Queensland, Australia.
authors.forename: C M
authors.initials: CM
authors.lastname: Wright
authors.forename: O F
authors.initials: OF
authors.lastname: Dent
authors.forename: M
authors.initials: M
authors.lastname: Barker
authors.forename: R C
authors.initials: RC
authors.lastname: Newland
authors.forename: P H
authors.initials: PH
authors.lastname: Chapuis
authors.forename: E L
authors.initials: EL
authors.lastname: Bokey
authors.forename: J P
authors.initials: JP
authors.lastname: Young
authors.forename: B A
authors.initials: BA
authors.lastname: Leggett
authors.forename: J R
authors.initials: JR
authors.lastname: Jass
authors.forename: G A
authors.initials: GA
authors.lastname: Macdonald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016019:Survival Analysis