Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer

Cancer Epidemiol Biomarkers Prev. 2017 Jan;26(1):61-67. doi: 10.1158/1055-9965.EPI-16-0215. Epub 2016 Sep 1.

Abstract

Background: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma.

Methods: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial.

Results: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I-II disease (HR=2.9; 95% CI, 1.2-6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy.

Conclusions: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment.

Impact: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61-67. ©2016 AACR.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Chromatin / genetics*
  • DNA / genetics*
  • Databases, Factual
  • Dilatation and Curettage / methods
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / mortality*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / surgery
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Norway
  • Ploidies
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Specimen Handling
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Chromatin
  • DNA