Focal lymphovascular space invasion: Friend or foe? A large retrospective analysis on stage I endometrioid endometrial carcinomas

• Published in: European journal of cancer (1990) Vol. 228; p. 115736
• Main Authors: Capasso, Ilaria, Perrone, Emanuele, Loverro, Matteo, Giannarelli, Diana, Nero, Camilla, Tortorella, Lucia, Esposito, Giovanni, Palmieri, Emilia, Zannoni, Gian Franco, Santoro, Angela, Salvati, Fabiana, Pirrelli, Fulvia, Fossatelli, Alessia, Mariani, Andrea, Fagotti, Anna, Fanfani, Francesco
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2025
• Subjects: Endometrial neoplasm; Immunohistochemistry; Lymphovascular space invasion; Molecular classification; Survival; Lymphovascular space invasion; Molecular classification; Immunohistochemistry; Endometrial neoplasm; Survival
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2025.115736

Literature is inconsistent with respect to clinical value of lymphovascular space invasion (LVSI) semiquantitative assessment. We aim to investigate the prognostic role of LVSI extent in stage I endometrioid endometrial carcinomas (ECs) classified by immunohistochemistry (IHC) analysis. Patients with stage I endometrioid EC undergone primary surgery were retrospectively included. Following World Health Organization definition for LVSI pathologic evaluation, subjects were divided into: LVSI-negative; LVSI-focal; LVSI-substantial. An IHC-based model was utilized to classify patients into: p53-aberrant (p53abn); mismatch repair deficient (MMRd); mismatch repair proficient with positive estrogen receptors (MMRp-ERpos); and mismatch repair proficient with negative estrogen receptors (MMRp-ERneg). 2091 subjects were included and divided into: 78.0 % (n:1631) LVSI-negative, 10.6 % (n:221) LVSI-focal, and 11.4 % (n:239) LVSI-substantial. Presence of LVSI (any extent) was associated with older age, larger tumor size and deeper myometrial infiltration. Patients with LVSI-substantial presented with higher incidence of grade 3 tumors, p53abn and MMRd status. Conversely, most LVSI-negative and LVSI-focal cases were MMRp-ERpos. At multivariable regression, LVSI-substantial was independently associated with reduced 5-year disease-free survival (DFS) and overall-survival (OS). LVSI-negative and LVSI-focal groups had similar DFS (p = 0.42) and OS (p = 0.09), whereas comparison with LVSI-substantial demonstrated significantly poorer outcomes for patients with substantial invasion. These findings were confirmed in sub-analyses of cases with grade 1–2 endometrioid and myometrial infiltration, and in the MMRp-ERpos cohort. In stage I endometrioid ECs, LVSI-focal was not associated with reduced oncologic outcomes compared to LVSI-negative. In contrast, LVSI-substantial was associated with aggressive clinicopathologic and molecular features and behaved as an independent prognostic factor for reduced survival. Our results were further confirmed in two low-risk EC settings: grade 1–2 with myometrial infiltration, and the MMRp-ERpos group. •Inconsistencies persist on the prognostic value of focal LVSI in stage I ECs.•Stage I endometrioid ECs with focal and negative LVSI have similar prognosis.•In contrast, endometrioid ECs with substantial LVSI had worse survival outcomes.•Sub-group analyses of ECs with very low-risk features confirmed these results.