Molecular biomarkers in endometrial hyperplasias predict cancer progression

Am J Obstet Gynecol. 2011 Apr;204(4):357.e1-12. doi: 10.1016/j.ajog.2010.12.007. Epub 2011 Feb 16.

Abstract

Objective: The purpose of this study was to assess the value of the 2003 World Health Organization (WHO) and endometrial intraepithelial neoplasia (EIN) classifications, D-score, and molecular biomarkers in endometrial hyperplasia (EH) for cancer progression.

Study design: We conducted a review of 307 endometrial hyperplasias for WHO and EIN classifications and an analysis of biomarkers, D-score, and cancer progression-free survival.

Results: The WHO, EIN, D-score, and many biomarkers were prognostic; 7.2% of the samples progressed to cancer. The WHO and EIN classifications correlated weakly with CK5/6 and p16. The D-score was strongest prognostically. When >1, it had the lowest false-negative progression rate of all features analyzed. COX2 negativity was the only other independent multivariate cancer progression predictor in endometrial hyperplasia, but only in cases with D-score <1. Eight of 13 cases (61%), with a combined D-score of <1 and negative COX2 progressed, which contrasted with 3 of 139 of all other cases (2.8%) (P < .0001; hazard ratio, 53.0). The biomarkers did not strengthen the prognostic value of the WHO or EIN classification.

Conclusion: Combined D-score <1 and COX2 negativity strongly predict cancer progression in endometrial hyperplasias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Carcinoma in Situ / classification
  • Carcinoma in Situ / pathology*
  • Cell Transformation, Neoplastic*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclooxygenase 2 / analysis
  • Endometrial Hyperplasia / classification
  • Endometrial Hyperplasia / pathology*
  • Endometrial Neoplasms / classification
  • Endometrial Neoplasms / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Keratin-5 / analysis
  • Keratin-6 / analysis
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Prognosis
  • World Health Organization

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Keratin-5
  • Keratin-6
  • Neoplasm Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human