PREDIKTIVNI ZNAČAJ EKSPRESIJE PROTEINA KLAUDIN-4 U UROTELNOM KARCINOMU MOKRAĆNE BEŠIKE BEZ ZAHVATANJA MIŠIĆNOG SLOJA
Klaudin-4 u urotelnom karcinomu mokraćne bešike
Sažetak
Klaudin-4 je integralni membranski protein tesnih spojeva epitelih ćelija, čija je ekspresija često izmenjena u karcinomima. Karcinom mokraćne bešike bez zahvatanja mišićnog sloja (engl. non-muscle-invasive urothelial bladder cancer – NMIBC) čest je tumor sa nepredvidivim kliničkim tokom koji zahteva precizniju prognostičku stratifikaciju i procenu rizika. Cilj ove studije bio je da se ispita povezanost između ekspresije klaudina-4 i kliničkopatoloških karakteristika NMIBC-a, kao i da se proceni prediktivni značaj klaudina-4 za prognozu bolesti. Studija je obuhvatila uzorke tumorskog tkiva 441 bolesnika sa urotelnim karcinomom bešike, koji su dobijeni transuretalnom resekcijom. Uzorci su inkorporirani u tkivne mikroareje i analizirani imunohistohemijski na ekspresiju klaudina-4. Visoka ekspresija uočena je kod 41,6% pTa i 47,8% pT1 tumora. Visoka ekspresija klaudina-4 značajno korelira sa visokim histološkim gradusom (p = 0,002) i pojavom hematurije (p = 0,038). Visoka ekspresija klaudina-4 bila je češća kod tumora sa divergentnom diferencijacijom ranih invazivnih karcinoma povezanih sa karcinomom in situ i rekurentnom bolešću. Međutim, ove povezanosti nisu bile statistički značajne. Kaplan‒Majerova analiza preživljavanja pokazala je da nije bilo značajne razlike u ukupnom preživljavanju između bolesnika sa visokom ekspresijom klaudina-4 i bolesnika sa niskom ekspresijom klaudina-4. Nasuprot tome, preživljavanje bez recidiva bolesti značajno je povezano sa ekspresijom klaudina-4 (p = 0,023). Može se zaključiti da je prekomerna ekspresija klaudina-4 povezana sa visokim tumorskim gradusom i kraćim preživljavanjem bez recidiva. Kao indikator agresivnog ponašanja tumora, klaudin-4 može poslužiti kao potencijalno koristan i pristupačan dodatak patohistološkom panelu za predviđanje kliničkog ponašanja karcinoma mokraćne bešike, a i kao i potencijalna meta ciljane terapije.
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