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

Heerik, Anne Sophie V M van den; Aiyer, K T S; Stelloo, Ellen; Jürgenliemk-Schulz, Ina M.; Lutgens, Ludy; Jobsen, Jan J.; Mens, Jan Willem M.; Steen-Banasik, Elzbieta M. van der; Creutzberg, Carien L.; Horeweg, Nanda; Bosse, Tjalling

doi:10.1016/j.ygyno.2022.06.027

Cited by 7 publications

(5 citation statements)

References 40 publications

(105 reference statements)

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“…However, in our cases of POLEmut, none of the patients showed recurrence. This is consistent with the study by van den Heerik et al (18), who observed 2 cases of POLEmut combined with MELF invasion and no disease recurrence. Studies have shown that the MELF pattern of MI plays a role in LVSI and LN metastasis, indicating the association of MELF patterns with epithelial-mesenchymal transformation (20).…”

supporting

confidence: 93%

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Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern

Ju,

Wu,

Sun

et al. 2023

International Journal of Gynecological Pathology

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The studies on the molecular classification of endometrioid carcinoma (EC) with microcystic, elongated, and fragmented (MELF) pattern invasion are limited. In this study, 77 cases of ECs with MELF patterns in Chinese women were collected. The molecular classification of the fifth edition of the World Health Organization was used to classify the molecular subtypes using immunohistochemistry staining (mismatch repair [MMR]-immunohistochemistry: MSH2, MSH6, MLH1, and PMS2; p53) and Sanger sequencing targeted POLE. The results showed that the prevalence of the 4 molecular subtypes in EC with MELF pattern was 6.5% (5/77) for POLE mutation, 20.8% (16/77) for MMR deficient, 11.7% (9/77) for p53-mutant, and 61.0% (47/77) for no specific molecular profile. The clinicopathological characteristics of each subtype were compared. The p53-mutant and no specific molecular profile subgroups were associated with higher International Federation of Gynecology and Obstetrics stage and International Federation of Gynecology and Obstetrics grade, deeper myometrial invasion, lymphovascular space invasion, lymph node metastasis, and absence of tumor-infiltrating lymphocytes, whereas the POLE mutation and MMR deficient subgroups were associated with lower aggressive features and prominent tumor-infiltrating lymphocytes. Progression-free survival showed that the p53-mutant and no specific molecular profile subgroups had a poorer prognosis than the POLE mutation and MMR deficient subgroups. However, lymph node metastasis was an independent factor associated with a higher risk of disease recurrence in multivariate analysis. In conclusion, ECs with MELF patterns can be divided into 4 molecular subtypes with discrepancies in aggressive clinicopathological characteristics and tumor-infiltrating lymphocytes. Molecular classification has clinical significance in a morpho-molecular approach for ECs with MELF patterns.

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confidence: 93%

“…The NSMP accounted for the highest proportion ( > 60%). A recent study found that NSMP accounted for 85.6% of early-stage EC with MELF pattern (18). The aggressive characteristics of the EC subgroups with MELF pattern were consistent with the molecular classifications of classic EC in this study.…”

supporting

confidence: 90%

Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern

Ju,

Wu,

Sun

et al. 2023

International Journal of Gynecological Pathology

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“…The latter manifests as variable-sized morules or solid sheets of eosinophilic cells with occasional keratinization, whereas the former is characterized by the presence of columnar or pseudostratified epithelial cells containing intracytoplasmic mucin. Three (6.0%) patients developed tumors that showed a microcystic, elongated, and fragmented pattern of myometrial invasion, which is characterized by loss of conventional glandular architecture, presence of squamoid or histiocyte-like cells with eosinophilic cytoplasm, formation of microcysts, compressed elongated structures, flattened and fragmented glandular epithelium, and an edematous or fibromyxoid stroma associated with an acute inflammatory response 25–29 .…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma

Lee,

Choi,

Kim

2023

International Journal of Gynecological Pathology

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Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.

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“…The MELF pattern of myometrial invasion is associated with a larger tumor size, a myometrial invasion of more than 50% of the uterine wall, a high number of LVI, lymph node metastasis, a papillary architecture, mucinous differentiation, and a higher risk of isolated tumor cells in sentinel lymph nodes of FIGO grade 1 EC [ 58 , 59 ]. PORTEC-1 and PORTEC-2 clinical trials have failed to show the independent impact of the MELF pattern on the risk of recurrence in early-stage EC [ 60 ].…”

Section: Lymphovascular Invasionmentioning

confidence: 99%

Uncommon Morphologic Types of Endometrial Cancer and Their Mimickers: How Much Does Molecular Classification Improve the Practice for Challenging Cases?

Saglam

2024

Life

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The previous endometrial cancer (EC) FIGO staging primarily relied on the extent of the disease spread into the anatomical sites at diagnosis. The most recent one (2023) incorporates clinicopathological features such as histological subtype, tumor grade, the extent of lymphovascular space invasion (LVI), and, when available, molecular subtypes of EC. The emphasis on accurate histological typing, tumor grading, and the molecular features of the cancer is stronger than ever. This review addresses challenging diagnostic patterns in the histologic subtyping and grading EC under five categories: 1. EC with spindle cells, 2. EC with clear cells, 3. EC with a papillary architecture, 4. EC with a biphasic morphology, and 5. EC with a microglandular architecture. The morphological features differentiating low- and high-grade cancers are discussed, along with relevant clinical work-ups. Recent molecular genetic findings regarding the diagnosis and prognosis of the disease and the results of related clinical trials are summarized. The potential challenges in the evaluation of LVI follow these sections. The final section of the review includes an overview of the literature on incorporating molecular subtypes of EC into clinical practice.

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

Cited by 7 publications

References 40 publications

Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern

Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma

Uncommon Morphologic Types of Endometrial Cancer and Their Mimickers: How Much Does Molecular Classification Improve the Practice for Challenging Cases?

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