Hormone Receptors May Help Predict Endometrial Cancer Survival and Recurrence, Review Finds

Endometrial carcinoma remains a prevalent female pelvic malignancy whose steady global rise is driven by metabolic risk factors, sedentary lifestyles, and extended life expectancy. While traditional frameworks like Bokhman's dualistic model and molecular profiling established baseline subtyping, non-standardized receptor evaluation created a clinical gap, prompting Dr. Bindhuja Joseph, Dr. Kitty Joseph Kuruvilla, and Dr. Arya Prakash from the Department of Pathology, Kanyakumari Medical Mission Research Centre, Tamil Nadu, India, to systematically evaluate the immunohistochemical expression of ER and PR to clarify their diagnostic, prognostic, and therapeutic utility.

Therefore, the systematic review analyzed 14 studies comprising 1,061 endometrial carcinoma (EC) patients to evaluate estrogen receptor (ER) and progesterone receptor (PR) expression across tumor grades and histological subtypes. After excluding non-English papers, case reports, and studies lacking immunohistochemistry (IHC) data, secondary endpoints assessed correlations with surgical stage, recurrence, and overall survival prognosis.

Key Clinical Findings of the Review Includes:

• Histological Subtype Differentiation: The review revealed that Type I endometrioid carcinomas strongly express ER and PR, whereas aggressive Type II serous carcinomas show weak or negative staining and carcinosarcomas demonstrate negative receptor expression.
• Tumor Grade Differentiation: The investigation demonstrated that Grade 1 tumors exhibit strong hormone receptor positivity and Grade 2 show moderate positivity, whereas Grade 3 poorly differentiated carcinomas consistently demonstrate negative or markedly reduced ER and PR levels.
• Survival and Recurrence Outcomes: The research confirmed that ER+/PR+ and ER-/PR+ status in Stage I disease significantly enhances 5-year survival rates and prolongs median survival in Stages II–IV compared to ER-/PR- tumors, with PR positivity showing a significant inverse correlation with disease recurrence.
• Quantitative Receptor Positivity: The review documented ER positivity rates ranging from 59.8% to 98% (e.g., Yadav et al. reported 98/100 ER+, p<0.01) and PR positivity rates between 60% and 98% across individual cohorts.
• Molecular and Epigenetics Interplay: The analysis highlighted that loss of ER and PR expression strongly correlates with p53 gene mutations present in high-grade lesions alongside PTEN inactivation and promoter hypermethylation.

The results suggest that robust estrogen receptor and progesterone receptor expression across 1,061 patient cases serves as a crucial prognostic biomarker that consistently identifies early-stage, low-grade tumors with favorable overall survival. Conversely, diminished or negative receptor status marks aggressive, high-grade non-endometrioid subtypes that exhibit higher recurrence rates and poor clinical outcomes.

Routine immunohistochemical assessment of ER and PR status allows clinicians to optimize individualized management plans, aiding in the selection of suitable candidates for conservative hormone therapy or fertility-sparing options while complementing molecular frameworks like The Cancer Genome Atlas (TCGA) and emerging artificial intelligence (AI) digital pathology workflows.

Although study design heterogeneity, sample size variations, and unstandardized immunohistochemical techniques currently constrain universal pooling, conducting prospective, multi-center investigations with standardized protocols will further validate these biomarkers and automated analytical technologies for universal clinical adoption.

Reference

Joseph B, Kuruvilla KJ, Prakash A. Decoding the role of hormonal receptors in the diagnosis and treatment of endometrial carcinoma: A systematic review. Indian J Pathol Oncol. 2026;13(3):206-211.