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Review
. 2023 Nov;44(6):392-400.
doi: 10.1007/s00292-023-01238-w.

[Molecular classification of endometrial carcinoma-a short summary for clinical use]

[Article in German]
Grit Gesine Ruth Hiller  1 , Anne Kathrin Höhn  2 , Doris Mayr  3   4 , Christine E Brambs  5 , Lars-Christian Horn  2   4
Affiliations
Review

[Molecular classification of endometrial carcinoma-a short summary for clinical use]

[Article in German]
Grit Gesine Ruth Hiller et al. Pathologie (Heidelb). 2023 Nov.

Erratum in

Abstract
in English, German

Background: Histopathological examination is still the backbone for the diagnosis and treatment decision making in endometrial carcinoma (EC). The binary classification of EC into type 1 (mostly endometrioid) and type 2 (mostly serous), although still helpful, showed overlapping clinical, morphological and molecular features and was not very prognostic discriminatory for all subtypes of EC.

Methods: Analysing the most recent studies dealing with the molecular classification of EC and the recommendations of the German S3-guidelines for EC.

Results and conclusion: Based on the comprehensive molecular study of The Cancer Genome Atlas Project (TCGA) four distinct molecular subtypes have been identified: EC with POLE mutation (POLEmut), with loss of mismatch repair proteins (MMR deficiency; dMMR), or with TP53 mutation (p53mut) and without any of these alterations, termed NSMP (no specific molecular profile). The molecular classification of EC presents a morphomolecular approach, based on histopathological evaluation (tumor diagnosis, subtyping, grading), immunohistochemistry (MMR, p53) and molecular analyses for POLE. The incorporation of this molecular classification is recommended for clinical use by the World Health Organisation (WHO) as well as many national guidelines and international societies. Due to the heterogeneity of NSMP-EC, which is the largest molecular group, additional research is indicated to further characterise these tumors.

Zusammenfassung: HINTERGRUND: Die histopathologische Diagnostik ist die Basis der Diagnostik und Therapie des Endometriumkarzinoms (EC). Die initial binäre Einteilung in Typ-1-EC (histopathologischer Prototyp endometrioid) bzw. Typ-2-EC (serös) hat sich als unzureichend trennscharf erwiesen.

Material und methoden: Es erfolgte eine selektive Recherche der Literatur und Analyse der Neuerungen der überarbeiteten Version der S3-Leitlinie Endometriumkarzinom.

Ergebnisse und schlussfolgerung: Basierend auf initialen Untersuchungen des The Cancer Genome Atlas Project (TCGA) sind 4 distinkte molekulare Subtypen des EC identifiziert worden: EC mit POLE-Mutation (POLEmut), mit Defizienz der Mismatch-Repair-Proteine (dMMR) oder mit p53-Mutation (p53mut) sowie solche ohne eine der genannten Veränderungen, NSMP („no special molecular profile“). Diese molekulare Klassifikation des EC erfolgt histologisch (Tumordiagnose, histologischer Subtyp, Grading), immunhistochemisch (MMR, p53) sowie molekularpathologisch (POLE) und stellt somit eine morphomolekulare Klassifikation dar. Entsprechend den Empfehlungen der Weltgesundheitsorganisation (WHO) sowie zahlreicher nationaler und internationaler Gesellschaften findet die molekulare Klassifikation des EC zunehmend Eingang in die klinische Versorgung. Bis dato unzureichend charakterisiert ist die große Gruppe der NSMP-EC.

Keywords: Classification; DNA mismatch repair; Endometrial neoplasms; Molecular biology; Mutation.

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References

Literatur

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