Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer

Floor J. Backes, Christopher J. Walker, Paul J. Goodfellow, Erinn M. Hade, Garima Agarwal, David Mutch, David E. Cohn, Adrian A. Suarez

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Background We sought to validate the prognostic significance of estrogen receptor alpha (ERα) expression and to investigate the relationship between ESR1 mutation status and outcomes in a large cohort of patients with endometrial cancer. We also investigated the predictive value of ERα for lymph node involvement in a large surgically staged cohort. Methods A tumor microarray (TMA) was constructed including only pure endometrioid adenocarcinomas, stained with ER50 monoclonal antibody, and assessed using digital image analysis. For mutation analysis, somatic DNA was extracted and sequenced for ESR1 gene hotspot regions. Differences in patient and tumor characteristics, recurrence and survival between ERα positive and negative, mutated and wild-type tumors were evaluated. Results Sixty (18.6%) tumors were negative for ERα. Absence of ERα was significantly associated with stage and grade, but not with disease-free or overall survival. ERα was a strong predictor of lymph node involvement (RR: 2.37, 95% CI: 1.12-5.02). Nineteen of 1034 tumors (1.8%) had an ESR1 hotspot mutation; twelve in hotspot 537Y, four in 538D and three in 536 L. Patients with an ESR1 mutation had a significantly lower BMI, but were comparable in age, stage and grade, and progression-free survival. Conclusion Patients with ERα negative endometrioid endometrial cancer are more often diagnosed with higher grade and advanced stage disease. Lymph node involvement is more common with lack of ERα expression, and may be able to help triage which patients should undergo lymphadenectomy. Mutations in ESR1 might explain why some low risk women with low BMI develop endometrial cancer.

Original languageEnglish
Pages (from-to)312-317
Number of pages6
JournalGynecologic oncology
Volume141
Issue number2
DOIs
StatePublished - May 1 2016

Keywords

  • Biomarker
  • ESR1
  • Endometrial cancer
  • Estrogen receptor alpha
  • Lymph node metastasis
  • Survival

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