Molecular subgroup-specific prognostic value of semiquantitative lymphovascular space invasion in early-stage endometrioid endometrial cancer

Objective

Molecular subgroups of endometrial carcinoma represent distinct disease entities, prompting subgroup-specific stratification. Recognizing lymphovascular space invasion (LVSI) as a key parameter in risk assessment, this study evaluates 3-tiered LVSI as a molecular subgroup-specific prognostic factor in stage I–II endometrioid endometrial cancer.

Methods

This retrospective study included patients treated at a single tertiary center. Immunohistochemistry and polymerase-ϵ (POLE) sequencing were conducted for molecular classification and determination of estrogen receptor and L1 cell adhesion molecule (L1CAM) expression.

Results

Among 843 eligible patients (median follow-up: 70 months), survival outcomes differed by molecular subgroup (P < 0.001 for progression-free survival and disease-specific survival). In MMRd carcinomas (n = 364), both focal (P < 0.001) and substantial (P < 0.001) LVSI were associated with poor progression-free survival. In NSMP carcinomas (n = 359), only substantial LVSI (P < 0.001) was prognostic (focal: P = 0.480). In p53abn carcinomas (n = 62), neither focal (P = 0.248) nor substantial (P = 0.484) LVSI showed prognostic significance. These findings remained after bivariate adjustments for stage (IA vs. IB vs. II), grade (low vs. high), estrogen receptor expression (3-tiered scale), L1CAM expression, age, and adjuvant therapy. Analysis was unfeasible for POLE ultramutated tumors (n = 58) due to a single progression.

Conclusion

The prognostic impact of 3-tiered LVSI varied by molecular subgroup in stage I–II endometrioid endometrial cancer, highlighting the need for subgroup-specific risk assessment to improve individualized counceling on treatment decisions and risk of progression.