HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status

Gynecol Oncol. 2021 Feb;160(2):514-519. doi: 10.1016/j.ygyno.2020.11.004. Epub 2020 Nov 16.

Abstract

Objectives: To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy.

Methods: Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios.

Results: 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001.

Conclusions: Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

Keywords: CA125; Endometrioid adenocarcinoma; HE4; Lymph node metastasis; Preoperative risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood*
  • Carcinoma, Endometrioid / blood
  • Carcinoma, Endometrioid / diagnosis*
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Endometrioid / surgery
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / diagnosis*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / surgery
  • Endometrium / pathology
  • Endometrium / surgery
  • Female
  • Humans
  • Hysterectomy
  • Lymph Node Excision / statistics & numerical data
  • Lymph Nodes / pathology
  • Lymph Nodes / surgery
  • Lymphatic Metastasis / diagnosis*
  • Lymphatic Metastasis / pathology
  • Membrane Proteins / blood*
  • Middle Aged
  • Neoplasm Grading / statistics & numerical data
  • Neoplasm Staging / statistics & numerical data
  • Predictive Value of Tests
  • Preoperative Period
  • ROC Curve
  • Reference Values
  • Retrospective Studies
  • Risk Assessment / methods
  • Salpingo-oophorectomy
  • WAP Four-Disulfide Core Domain Protein 2 / analysis*

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • MUC16 protein, human
  • Membrane Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human