Stratification of intermediate-risk endometrial cancer patients into groups at high risk or low risk for recurrence based on tumor gene expression profiles

Clin Cancer Res. 2005 Mar 15;11(6):2252-7. doi: 10.1158/1078-0432.CCR-04-1353.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / therapy
  • Female
  • Gene Expression Profiling*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / genetics
  • Neoplasm Recurrence, Local* / metabolism
  • Neoplasm Recurrence, Local* / therapy
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Risk Factors

Substances

  • Biomarkers, Tumor