Objectives To evaluate the distribution of LVSI and LNM according to the EC molecular classification.

Methods Patients with EC surgically treated were retrospectively analyzed. Tumor grade and histologic subtype were assessed by HE technique. MMR and p53 status were assessed by IHC in all patients. POLE was sequentiated in 6 LCN G3 patients. Chi-square test was adopted for categorical data. Odds-ratio was adopted to evaluate association.

Results 70 consecutive patients entered the study: endometrioid type was found in 61 (87.1%); G1–2 in 44 (62.9%) and G3 in 26 (37.1%) patients, respectively. Molecular profiling classified 3 (4.3%) as POLE-ultramutated, 34 (48.6%) as LCN, 22 tumors (31.4%) as MMRd and 11 (15.7%) as p53-mutated. LVSI was found in 18 (25.7%) patients: 0/3 (0%) u-POLE, 6/34 (17.6%) LCN, 6/22 (27.3%) MMRd and 6/11 (54.5%) p53-mutated (p = 0,07). LNM were present in 17 (24.3%) cases: 0/3 (0%) u-POLE, 5/34 (14.7%) LCN, 5/22 (22.7%) MMRd and 7/11 (63.6%) p53-mutated (p < 0,01). MMRd vs LCN: OR 1.75 (95% CI 0.48–6.34, p=0.39) for LVSI and 1.70 (95% CI 0.43–6.75, p=0.44) for LNM.

Conclusions The rate of LVSI and LNM showed a significantly increasing trend from u-POLE to p53-mutated. Among the MMRd and LCN molecular subtypes with intermediate prognostic impact, where the classical prognostic parameter may have a role, MMRd patients had a higher, although not significant, risk of LVSI and LNM. The reduced number of patients, which is one of the limit of the study may explain the lack of significance. Larger studies are suggested.