title: Stratification of intermediate-risk endometrial cancer patients into groups at high risk or low risk for recurrence based on tumor gene expression profiles.
abstract: OBJECTIVE
  Endometrial cancers classified as "intermediate risk" based on clinical and/or pathologic features are associated with a 15% to 20% risk of recurrence. Here, we test whether global gene expression profiling can distinguish intermediate-risk tumors into high-risk and low-risk subgroups.
  
  
  METHODS
  Tumor specimens were obtained from 75 intermediate-risk endometrial cancer patients, 13 who had recurred and 62 who had not recurred with a median follow-up of 24 months. Gene expression profiles were obtained using the Affymetrix U133A GeneChip oligonucleotide microarray. The genes most associated with risk of recurrence were used to create a risk score using a leave-one-out cross-validation method and the univariate Cox proportional hazards regression model. Time to recurrence curves for the high-risk and low-risk subgroups were estimated using the Kaplan-Meier method, and the difference in time to recurrence between these two subgroups was tested using the log-rank test.
  
  
  RESULTS
  There was a significant difference in time to recurrence between high-risk and low-risk patients using risk scores as defined above (P = 0.04). The estimated hazard ratio (95% confidence interval) was 3.07 (1.00-9.43).
  
  
  CONCLUSIONS
  Patients with intermediate-risk endometrial cancers identified as high-risk for recurrence according to a gene expression-based risk score have a significantly increased risk for recurrence compared with those classified as low risk. These findings suggest that gene expression profiling can potentially contribute to the clinical classification and management of intermediate-risk endometrial cancers.
authors.affiliation: Departments of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ferguson
authors.forename: Adam B
authors.initials: AB
authors.lastname: Olshen
authors.forename: Agnès
authors.initials: A
authors.lastname: Viale
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor