HISTOPATOLOŠKE I MOLEKULARNE KARAKTERISTIKE KOLOREKTALNOG KARCINOMA – OSVRT NA ZNAČAJ EPITELNO-MEZENHIMALNE TRANZICIJE

Aleksandra Đikić Rom; Goran Barišić

doi:10.5937/mp75-45064

Aleksandra Đikić Rom University Clinical Centre of Serbia, Department of pathology, pathohistology and medical cytology, Belgrade, Serbia
Goran Barišić Univerzitetski Klinčki centar Srbije, Beograd, Srbija; Medicinski Fakultet Univerziteta u Beogradu, Srbija

DOI: https://doi.org/10.5937/mp75-45064

Ključne reči: kolorektalni karcinom, epitelno-mezenhimalna tranzicija, mezenhimalno-epitelna tranzicija, tumorsko pupljenje, molekularna klasifikacija

Sažetak

Kolorektalni karcinom (CRC) je treći po učestalosti najčešće dijagnostikovani karcinom

i drugi je najčešći uzrok smrti kada su u pitanju maligne neoplazme, uključujući oba pola.

Najznačajniji prognostički i prediktivni faktori za CRC su histološki tip i gradus tumora, TNM

stadijum tumorske bolesti, limfo-vaskularna i perineuralna infiltracija, tumorsko pupljenje i

rezidulani status. Molekularna klasifikacija CRC-a zasnovana je na njegovim genetskim

karakteristikama, ćelijskim specifikacijama, mikrookruženju karcinoma i imunološkim

karakteristikama, i od velikog je praktičnog značaja, jer se pojedini podtipovi razlikuju po svom

kliničkom toku i različito reaguju na hemoterapeutski i biološki tretman. Epitelno-mezenhimalna

tranzicija (EMT) je proces transdiferencijacije u kome epitelne ćelije dobijaju osobine koje su

karakteristične za mezenhimalne ćelije. Tokom neoplastične progresije, karcinomske ćelije

dobijaju genetske i epigenetske karakteristike koje utiču na onkogene i tumor supresorne gene,

što na kraju rezultira aktivacijom programa tipa III EMT-e, dajući im potencijal za invaziju i

metastaziranje, doprinoseći stemness-u karcinomskih ćelija, njihovoj otpornosti na lekove i

izbegavanju imunološkog odgovora. Promene nastale u ćelijama, tokom EMT-e, mogu biti

reverzibilne po dolasku na pogodnu lokaciju za kolonizaciju, procesom suprotnim od EMT-e,

koji se naziva mezenhimalno-epitelna tranzicija (MET), tokom kojeg ćelije vraćaju karakteristike

epitelnog fenotipa. Kod većine humanih tipova karcinoma, potpuno pomeranje sa epitelnog na

mazenhimalni fenotip tokom EMT se retko sreće, već većina karcinoma pokazuje parcijalnu

EMT-u. Ćelije koje prolaze kroz parcijalnu EMT se teško identifikuju, zbog svoje fenotipske

heterogenosti i varijabilne ekspresije markera EMT-e. Neophodno je pronalaženje novih

biomarkera EMT-e, naročito parcijalne EMT-e, kao i bolje razumevanje odnosa EMT-e i

rezistencija na terapiju, u cilju razvoja novih terapijskih pristupa za CRC.

Biografije autora

Aleksandra Đikić Rom, University Clinical Centre of Serbia, Department of pathology, pathohistology and medical cytology, Belgrade, Serbia

Specijalista patološke anatomije, Odeljenje za digestivnu, abdominalnu i urgentnu patologiju, Službe za patologiju, patohistologiju i medicinsku citologiju, Univerzitetskog Kliničkog centra Srbije

Goran Barišić, Univerzitetski Klinčki centar Srbije, Beograd, Srbija; Medicinski Fakultet Univerziteta u Beogradu, Srbija

vanredni profesor na katedri predmeta Hirurgija sa anesteziologijom, Medicinski fakultet Univerziteta u Beogradu, Klinici za digestivnu hirurgiju, Univerzitetski Klnički centar Srbije , Beograd, Srbija

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