| Title: |
PREDICTIVE VALUE OF CLAUDIN-4 EXPRESSION IN NON-MUSCLE INVASIVE UROTHELIAL BLADDER CANCER. |
| Alternate Title: |
PREDIKTIVNI ZNAČAJ EKSPRESIJE PROTEINA KLAUDIN-4 U UROTELNOM KARCINOMU MOKRAĆNE BEŠIKE BEZ ZAHVATANJA MIŠIĆNOG SLOJA. |
| Authors: |
Stojnev, Slavics1,2 slavicastojnev@gmail.com, Ristić-Petrović, Ana1,2, Radić, Milica3,4, Janković Veličković, Ljubinka1,2 |
| Source: |
Acta Medica Medianae. Dec2024, Vol. 63 Issue 4, p114-121. 8p. |
| Subject Terms: |
*NON-muscle invasive bladder cancer, *STATISTICAL significance, *TRANSITIONAL cell carcinoma, *BLADDER cancer, *OVERALL survival |
| Abstract (English): |
Claudin-4 is an integral membrane protein of tight junctions, and its expression is frequently altered in epithelial cancers. Non-muscle-invasive urothelial bladder cancer (NMIBC) is a common neoplasm with an unpredictable clinical course that requires more precise stratification and risk assessment. The aim of this study was to investigate the association between Claudin-4 expression and clinicopathologic features of NMIBC, and to assess the predictive impact of Claudin-4 regarding to disease prognosis. The study comprised tumor tissue samples obtained from 441 patients with urothelial bladder cancer who had undergone transurethral resection. Samples were embedded in tissue microarrays and analyzed immunohistochemically for Claudin-4 expression. High expression was found in 41.6% of pTa and 47.8% of pT1 tumors. High Claudin-4 expression significantly correlated to high histologic grade (p = 0.002), and hematuria (p = 0.038). High Claudin-4 expression was more frequently observed in tumors with divergent differentiation, early invasive cancers associated with carcinoma in situ, and recurrent disease, however, these associations were not statistically significant. Kaplan--Meier survival analysis failed to indicate a significant difference in overall survival between the patients with high and low Claudin-4 expression. Conversely, recurrence-free survival was significantly associated with Claudin-4 expression (p = 0.023). In conclusion, overexpression of Claudin-4 is associated with high tumor grade and shorter recurrence-free survival. As an indicator of aggressive tumor behavior, Claudin-4 may serve as a potentially useful and accessible addition to the pathohistological panel for the prediction of clinical behavior of urothelial bladder cancer, as well as a promising therapeutic target. [ABSTRACT FROM AUTHOR] |
| Abstract (Serbian): |
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. [ABSTRACT FROM AUTHOR] |
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