NOVI MOLEKULARNI BIOMARKERI U KARCINOMU ENDOMETRIJA – POGLED PATOLOGA. (Croatian)

NEW MOLECULAR BIOMARKERS IN ENDOMETRIAL CARCINOMA – VIEW OF PATHOLOGIST. (English)

Introduction: Endometrial carcinoma is the most common malignant tumor occurring in the female genital tract. Histologically, it can be endometrioid carcinoma, serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, mixed carcinoma and carcinosarcoma. Endometrioid endometrial carcinoma is the most prevalent type, accounting for 80% of cases. The prognostic factors for endometrial carcinoma include histological grade, depth of myometrial invasion, serosal, cervical stromal, vaginal, or adnexal invasion, along with lymphovascular invasion and lymph node status. However, it is challenging to predict tumor aggressiveness in endometriod carcinoma with the same histological grade and prognostic factors. Therefore, additional prognostic parameters are essential to identify tumors with a poor prognosis. Objectives: The latest WHO Classification of female genital tumors from 2020 divides endometrioid endometrial carcinoma (EEC) into four molecular subtypes. These subtypes include: endometrioid adenocarcinoma of mutated DNA polymerase epsilon (POLE ultramutated), endometrioid adenocarcinoma with mismatch repair deficiency (MMRd), p53-mutated endometrioid adenocarcinoma, and endometrioid adenocarcinoma with nonspecific molecular profile (NSMP). The p53-mutated endometrioid adenocarcinoma subtype is present in 2–5% of all low-grade EEC and 20% of high-grade EEC, making it the subtype with the worst prognosis and the shortest time to relapse. Changes in MMR and p53 proteins can be determined with immunohistochemistry. The molecular classification has been included in the 2023 FIGO classification of endometrial tumors. Conclusion: The identification of molecular biomarkers, such as the subtypes of EEC, is crucial in determining the tumor aggressiveness and the appropriate oncological treatment. This perspective opens doors for further research to discover other prognostic parameters and offer promising prospects for improving the diagnosis and treatment of endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Uvod: Endometralni karcinom je najčešća zloćudna novotvorina ženskog spolnog sustava. Histološki razlikuju se endometrioidni karcinom, serozni karcinom, svijetlo-stanični karcinom, nediferencirani karcinom, dediferencirani karcinom, miješani karcinom i karcinosarkom. Endometrioidni endometralni karcinom (EEC) je najčešći histološki tip karcinoma obuhvaćajući 80% slučajeva. Prognostički čimbenici za endometralni karcinom uključuju histološki gradus, dubinu invazije miometrija, zahvaćanje seroze, cervikalne strome, vagine ili adneksa te limfovaskularnu invaziju i zahvaćenost limfnih čvorova. Usprkos postojećim prognostičkim čimbenicima, teško je predvidjeti agresivnost endometrioidnog karcinoma u skupini karcinoma istog histološkog gradusa i istih prognostičkih čimbenika. Iz tog razloga, potrebni su dodatni prognostički parametri kako bismo otkrili tumore s lošom prognozom. Predmet predavanja: Zadnja Klasifikacija tumora ženskog spolnog sustava Svjetske zdravstvene organizacije objavljena 2020. godine dijeli endometrioidne adenokarcinome endometrija (EEC) u četiri molekularna podtipa. Ti podtipovi su: POLE (patogene somatske mutacije krivog smisla u egzonukleaznoj domeni epsilon DNA polimeraze) mutirani endometrioidni adenokarcinom, endometrioidni adenokarcinom s deficijencijom proteina za popravak krivo sparenih baza (eng. mismatch repair deficient MMRd), p53-mutirani endometrioidni adenokarcinom i endometrioidni adenokarcinom nespecifičnog molekularnog profila (NSMP). Podtip p53-mutirani endometrioidni adenokarcinom čini 2–5% svih EEC niskog gradusa i 20% svih EEC visokog gradusa i predstavlja podtip s najlošijom prognozom i najkraćim vremenom do povrata bolesti. Promjene MMR i p53 proteina mogu se određivati imunohistokemijski. Molekularna klasifikacija endometrioidnog karcinoma je uključena u FIGO 2023 klasifikaciju endometralnih tumora. Zaključak: Otkrivanje molekularnih biomarkera, poput molekularnih podtipova karcinoma endometrija, je ključno u predviđanju agresivnosti tumora i odgovarajućeg onkološkog liječenja. Takva perspektiva otvara vrata sljedećim istraživanjima u otkrivanju novih parametara koji će omogućiti još bolju perspektivu za potvrdu dijagnoze i odabir adekvatnog onkološkog liječenja. [ABSTRACT FROM AUTHOR]

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