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Background <p>Endometrial carcinoma (EC) molecular subtypes are critical for risk assessment and treatment guidance, with strong prognostic implications.</p> Objectives <p>To investigate associations between EC molecular subtypes and high-risk pathological factors to optimize individualized therapy.</p> Design <p>Multicenter retrospective cohort study.</p> Methods <p>Retrospective analysis of 292 EC cases classified via the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) into four subtypes: POLE ultramutant (POLE-mut), mismatch repair deficient (MMRd), p53 abnormal (p53 abn), and p53 wild-type (p53 wt). Associations with clinicopathological parameters were assessed using chi-square tests and logistic regression.</p> Results <p>Among the 292 patients, the distribution of molecular subtypes was as follows: POLE-mut (6.8%), MMRd (21.2%), p53 abn (14.4%), and p53 wt (57.5%). Molecular subtypes correlated significantly with International Federation of Gynecology and Obstetrics (FIGO) stage (p &lt; 0.001), poor/undifferentiated histology (p &lt; 0.001), and lymphovascular space invasion (LVSI) (p = 0.001). The POLE-mut and p53 wt were predominantly enriched in stage I disease (90.0% and 80.4%, respectively). In contrast, the majority of p53 abn were classified as stage II (81.0%). The MMRd subtype was distributed across all stages. Advanced stages (III-IV) were most frequently observed in the p53 abn and MMRd subtypes. p53 abn showed the highest rate of poor/undifferentiated histology (61.9%). MMRd comprised the largest proportion of LVSI-positive cases (39.1%). Multivariate analysis identified MMRd as an independent predictor of LVSI (p = 0.001), while both MMRd (p = 0.009) and p53 abn (p &lt; 0.001) independently predicted poor/undifferentiated histology.</p> Conclusions <p>EC molecular subtypes stratify clinicopathological risk and predict tumor behavior, highlighting their potential utility in informing individualized management. These findings suggest possible roles ranging from treatment de-escalation (POLE‑mut) to treatment intensification (p53‑abn), although further prospective studies are needed before routine clinical implementation.</p>

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Associations between molecular subtypes and high-risk pathological factors in endometrial cancer

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Xueqing Sun,
  • Jing Xue,
  • Zhen Sun,
  • Wei Tian,
  • Xiao Song,
  • Ran Chu,
  • Ming Liu

摘要

Background

Endometrial carcinoma (EC) molecular subtypes are critical for risk assessment and treatment guidance, with strong prognostic implications.

Objectives

To investigate associations between EC molecular subtypes and high-risk pathological factors to optimize individualized therapy.

Design

Multicenter retrospective cohort study.

Methods

Retrospective analysis of 292 EC cases classified via the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) into four subtypes: POLE ultramutant (POLE-mut), mismatch repair deficient (MMRd), p53 abnormal (p53 abn), and p53 wild-type (p53 wt). Associations with clinicopathological parameters were assessed using chi-square tests and logistic regression.

Results

Among the 292 patients, the distribution of molecular subtypes was as follows: POLE-mut (6.8%), MMRd (21.2%), p53 abn (14.4%), and p53 wt (57.5%). Molecular subtypes correlated significantly with International Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.001), poor/undifferentiated histology (p < 0.001), and lymphovascular space invasion (LVSI) (p = 0.001). The POLE-mut and p53 wt were predominantly enriched in stage I disease (90.0% and 80.4%, respectively). In contrast, the majority of p53 abn were classified as stage II (81.0%). The MMRd subtype was distributed across all stages. Advanced stages (III-IV) were most frequently observed in the p53 abn and MMRd subtypes. p53 abn showed the highest rate of poor/undifferentiated histology (61.9%). MMRd comprised the largest proportion of LVSI-positive cases (39.1%). Multivariate analysis identified MMRd as an independent predictor of LVSI (p = 0.001), while both MMRd (p = 0.009) and p53 abn (p < 0.001) independently predicted poor/undifferentiated histology.

Conclusions

EC molecular subtypes stratify clinicopathological risk and predict tumor behavior, highlighting their potential utility in informing individualized management. These findings suggest possible roles ranging from treatment de-escalation (POLE‑mut) to treatment intensification (p53‑abn), although further prospective studies are needed before routine clinical implementation.