Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials

A. S.V.M. van den Heerik, K. T.S. Aiyer, E. Stelloo, I. M. Jürgenliemk-Schulz, L. C.H.W. Lutgens, J. J. Jobsen, J. W.M. Mens, E. M. van der Steen-Banasik, C. L. Creutzberg, V. T.H.B.M. Smit, N. Horeweg, T. Bosse*

*Corresponding author for this work

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Objective: Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of MELF invasion was uncertain due to conflicting data, and it had not yet appropriately been studied in the context of the molecular EC classification. We aimed to determine the relation of MELF invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early-stage low/intermediate risk EC. Methods: Single whole tumor slides of 979 (85.8%) out of 1141 (high)intermediate-risk EC of women who participated in the PORTEC-1/−2 trials were available for review. Clinicopathological and molecular features were compared between MELF invasion positive and negative cases. Time-to-event analyses were done by Kaplan-Meier method, log-rank tests and Cox’ proportional hazards models. Results: MELF invasion was found in 128 (13.1%) cases, and associated with grade 1–2 histology, deep myometrial invasion and substantial lymph-vascular space invasion (LVSI). 85.6% of MELF invasion positive tumors were no-specific-molecular-profile (NSMP) EC. NSMP EC with MELF invasion were CTNNB1 wild type in 92.2% and KRAS mutated in 24.4% of cases. Risk of recurrence was lower for MELF invasion positive as compared to MELF invasion negative cases (4.9% vs. 12.7%, p = 0.026). However, MELF invasion had no independent impact on risk of recurrence (HR 0.65, p = 0.30) after correction for clinicopathological and molecular factors. Conclusions: MELF invasion has no independent impact on risk of recurrence in early-stage EC, and is frequently observed in low-grade NSMP tumors. Routine assessment of MELF invasion has no clinical implications and is not recommended.

Original languageEnglish
Pages (from-to)530-537
Number of pages8
JournalGynecologic Oncology
Issue number3
Early online date12 Jul 2022
Publication statusPublished - 1 Sept 2022

Bibliographical note

Funding Information:
ASVMvdH, NH and CLC report a grant from the Dutch Cancer Society (unrelated). NH reports grant from Varian (unrelated), CLC reports grants from Varian (unrelated) and Elekta (non-financial, unrelated), IDMC membership Merck (unrelated) and chair Endometrial committee CGIG.

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