[Predictive significance of microcystic elongated and fragmented (MELF) growth pattern in the prognosis of no specific molecular profile endometrial endometrioid carcinoma]

Objective: To investigate the association between the microcystic, elongated, and fragmented (MELF) growth pattern and the prognosis of no specific molecular profile endometrial endometrioid carcinoma (NSMP-EEC). Methods: A retrospective study was conducted on 911 NSMP-EEC patients diagnosed at the Pathology Department of Peking University Third Hospital from January 2015 to September 2023. Complete hysterectomy specimens were obtained from these patients. Utilizing sanger sequencing, next generation sequencing and immunohistochemical techniques, we conducted endometrial carcinoma molecular classification according to WHO 2020 criteria, and identified clinical staging based on the International Federation of Gynecology and Obstetrics (FIGO) 2023 criteria. The primary endpoints were progression-free survival and disease-specific survival. Patients were divided into MELF (+) and MELF (-) groups based on the presence or absence of the MELF growth pattern, and clinicopathological characteristics were compared between the two groups. Kaplan-Meier survival curves were used to analyze the association between the MELF growth pattern and prognosis, and log-rank tests were performed to compare differences between groups. Results: The age of the 911 patients was (54.4±10.7) years, with a follow-up time [M (Q1,Q3)] of 24.0 (11.0, 41.0) months, and of which 147 patients (16.1%) belonged to the MELF (+) group. The MELF (+) group had a higher proportion of postmenopausal patients and G1/G2, deep myometrial invasion, lymphovascular space invasion, and lymph node metastasis, higher FIGO stages, higher ESGO risk groups, and higher tumor recurrence rates compared to the MELF (-) group (all P<0.05). The cumulative 5-year progression-free survival rate for MELF (-) and MELF (+) patients were 92.2% and 85.8%, respectively (P=0.015). In the G1/G2 NSMP-EEC cohort, the cumulative 5-year progression-free survival rate for MELF (-) and MELF (+) patients were 94.2% and 86.6%, respectively (P=0.003). The prognosis of NSMP-EEC patients with 2023 FIGO stage I was better, exhibiting a cumulative 5-year progression-free survival rate of 95.2% and a cumulative 5-year disease-specific survival rate of 99.1%, respectively, and MELF (+) was not associated with a decrease in either the cumulative progression-free survival rate (P=0.213) or the cumulative disease-specific survival rate (P=0.373) of patients. Conclusions: In NSMP-EEC patients, MELF (+) is associated with various adverse clinicopathological indicators and increased recurrence risk, providing a simple and rapid morphological indicator for risk stratification. The prognosis of NSMP-EEC patients with 2023 FIGO stage Ⅰis better, and the use of MELF alone is insufficient for risk stratification.