A recent study supported incorporating routine evaluation of ER and PR expression, in addition to molecular subgroup, in patients with endometrial cancer.

Study findings published in Gynecologic Oncology showed that estrogen and progesterone (ER/PR) expression remains prognostically relevant across molecular subgroups of patients with endometrial cancer (EC) and that a three-tiered cutoff improves prognostication.

Stephanie W. Vrede, MD, and colleagues conducted a retrospective multicohort study using data from the European Network for Individualized Treatment centers and Vancouver Hospital, Canada. ER/PR immunohistochemical (IHC) expression was grouped as ER/PR 0-10%, 20-80%, or 90-100%. Full next-generation sequencing and immunohistochemistry were used to determine molecular subgroups: POLEmut, mismatch repair deficient (MMRd), p53mut, and no-specific molecular profile (NSMP).

Patients with EC and known and classifiable ER/PR ICH status numbered 739 were included. The median age of the cohort was 65 years, with a median BMI of 29 kg/m² and a median follow-up of 60 months. Tumors were classified as POLEmut in 9.1% (n=67), MMRd in 27.6% (n=204), p53mut in 20.8% (n=154), and NSMP in 42.5% (n= 314).

Among all molecular subgroups, patients with ER/PR 90-100% expression exhibited the best 5-year disease-specific survival (DSS). Among those with POLEmut and MMRd tumors, patients did not have significantly different 5-year DSS within the three subgroups of PR expression.

Interestingly, the researchers noted that patients with p53mut EC and PR 90-100% expression had a 5-year DSS of 100% compared with PR 20-80% (62%; P=0.032) and PR 0-10% (48%; P=0.006).

Within NSMP tumors, the 5-year DSS was 98% for patients with PR 90-100%, 88% for PR 20-80%, and 56% for PR 0-10%.

ER expression is prognostically more relevant in MMRd and NSMP tumors. For MMRd tumors, patients with ER 90-100% and 20-80% or 0-10% expression showed significantly different 5-year DSS (96.0 % vs 80.0 %; P=0.017 and 96.0 % vs 71.0%; P=0.002, respectively). Within NSMP tumors, patients with ER 0-10% expression had a significantly worse 5-year DSS of 48% compared with ER 90-100% and ER 20-80% expression (96% and 88%, respectively; P<0.001).

Across all molecular subgroups, PR 0-10% expression, p53mut, lymphovascular space invasion, and International Federation of Gynecology and Obstetrics stage III-IV remained independently prognostic for reduced DSS. However, PR 90-100 % and POLEmut stayed independently prognostic for improved DSS.

“This study demonstrates the prognostic importance of ER and PR biomarkers within the era of molecular profiling and the relevance of a three-tiered risk classification,” said the researchers. “These data support incorporating routine evaluation of ER/PR expression in clinical practice.”