The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification

J Gynecol Oncol. 2019 Jan;30(1):e13. doi: 10.3802/jgo.2019.30.e13. Epub 2018 Oct 29.

Abstract

Objectives: Although patients with grade I and II endometrioid endometrial adenocarcinoma (EEA) are considered with good prognosis, among them 15%-25% died in 5 years. It is still unknown whether integrating estrogen receptor (ER) and progesterone receptor (PR) into clinical risk stratification can help select high-risk patients with grade I-II EEA. This study was to investigate the prognostic value of ER and PR double negativity (ER/PR loss) in grade I-II EEA, and the association between ER/PR loss and The Cancer Genome Atlas (TCGA) classification.

Methods: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I-II EEA. ER and PR negativity were determined when <1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network.

Results: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21-12.52) and overall survival (OS; HR=7.59; 95% CI=2.55-22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60-10.14) and OS (HR=5.56; 95% CI=1.37-22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28-23.89) and stage II-IV (n=129; HR=5.77; 95% CI=1.57-21.27). No association was found between ER/PR loss and TCGA classification.

Conclusion: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I-II EEA patients.

Keywords: Biomarker; Endometrial Cancer; Endometrioid Carcinoma; Estrogen Receptor; Low-Grade; Progesterone Receptor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Predictive Value of Tests
  • Progression-Free Survival
  • Proportional Hazards Models
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone