Molecular classification and adjuvant treatment in endometrioid endometrial cancer with microcystic elongated and fragmented (MELF) invasion pattern.

Objective: To assess the characteristics, molecular classification, and role of adjuvant treatment in patients with endometrioid endometrial cancer (EEC) and microcystic elongated and fragmented (MELF) myometrial invasion pattern.

Methods: This study included patients who were diagnosed with EEC with a MELF invasion pattern and underwent surgery from January 2019 to December 2023. We analyzed molecular classification, clinicopathological characteristics, and prognostic outcomes, including recurrence and adjuvant therapy.

Results: Out of 529 patients, 84 (15.9%) exhibited the MELF pattern, with 1 (1.2%) classified as POLE-mutation, 19 (22.6%) as mismatch repair deficient, 53 (63.1%) as no specific molecular profile, and 11 (13.1%) as p53-mutant subtype. Fifty (59.5%) patients with MELF invasion pattern received adjuvant chemotherapy (CT) ± external beam radiation therapy (EBRT), 19 (22.6%) received EBRT only, and 15 (17.9%) received no adjuvant treatment. Receiving adjuvant therapy was significantly associated with the risk level defined by the ESMO guideline for endometrial cancer (p = 0.002). With a median follow-up of 26 months (range: 1-59), the progression-free survival at 3-years for the MELF invasion patients was 91%. Seven patients with the MELF pattern experienced recurrence, of whom one was in stage IA (low risk, local recurrence) and did not receive any additional treatment, two were in stage IB (intermediate / high-intermediate risk, distant recurrence) and received EBRT only and the remaining four were in stage III to IV and had distant recurrence despite receiving adjuvant chemotherapy with or without EBRT. Among 43 intermediate- and high-intermediate-risk EEC patients, receiving CT ± EBRT was significantly associated with better DFS than without CT (p = 0.047).

Conclusion: The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type.