Baranović, Sandra, Lukšić, Ivica, Manojlović, Spomenka, Čupić, Hrvoje, Vagić, Davor, and Ćorić, Marijana
Uvod: Hedgehog (HH) signalni put uključen je u embrionalni razvoj, proliferaciju i diferencijaciju stanica brojnih tkiva, te regulira epitelno-mezenhimni prijelaz (EMT) stanica uz pomoć liganada HH (SHH, PTCH, SMO i GLI1). Iako su molekule HH pojačano izražene u različitim zloćudnim tumorima, nije dovoljno poznata prognostička vrijednost njihove izraženosti u planocelularnom karcinomu usne šupljine. Ispitanici i metode: Istraživanje je uključilo 120 bolesnika s karcinomom usne šupljine kliničkog stadija T1-T3N0 koji su primarno kirurški liječeni u razdoblju od 1. siječnja 2006. do 31. prosinca 2010. godine. Ovim istraživanjem određena je izraženost molekula Hedgehoga signalnoga puta u planocelularnom karcinomu usne šupljine imunohistokemijskim postupkom i semikvantitativnom analizom. Dobiveni rezultati korelirani su s kliničkim i histološkim prognostičkim obilježjima, pojavom recidiva bolesti i doživljenjem bolesnika. Rezultati: Ispitivana skupina brojila je 99 (82,5 %) muškaraca i 21 (17,5 %) ženu, prosječne dobi 59 godina. Procijenjeno 5-godišnje doživljenje je bilo 85 %. Tijekom praćenja, umrlo je 18 bolesnika, a 102 je cenzorirano. Procijenjeno 5-godišnje doživljenje bez bolesti jest 53,33%. U razdoblju praćenja 50 bolesnika razvilo je recidiv bolesti. SHH je dokazan u uzorcima 116 (96,7 %) bolesnika, PTCH u 104 (86,7 %), SMO u 103 (85,8 %), GLI1 u 72 (60 %) bolesnika. Stupanj izraženost HH proteina nije bio značajno povezan s ispitivanim kliničkim ili histološkim obilježjima. Jednako tako, izraženost molekula Hedgehoga signalnoga puta nije povezana s pojavom recidiva bolesti i s duljinom doživljenja, osim SHH za koji se izraženost u tumoru pokazala kao statistički značajan čimbenik za ukupno doživljenje bolesnika (c2=6,74, P=0,034). Zaključci: S obzirom na to da biološko ponašanje tumora ne ovisi o jačini izraženosti molekula signalnog puta HH, rutinsko određivanje njihove izraženosti u karcinomu usne šupljine, metodom imunohistokemije, nije opravdano. Čimbenici koji su utjecali na prognozu i ishod bolesti, odnosno OS i DFS, su lokalni i regionalni recidiv karcinoma, udaljene metastaze, prisutnost okultnih metastaza u trenutku primarnog liječenja i proboj čahure limfnog čvora., Introduction: Hedgehog signaling pathway is involved in embrionic development, proliferation and differentiation of cells and tissues. It also regulates epithelial-mesenchimal transition (EMT) through activation of SHH, PTCH, SMO and GLI1. Overexpression of Hedgehog signaling pathway proteins has been shown in various malignant tumors. However, the prognostic significance of its expression in oral squamous cell carcinoma (OSCC) is still not known enough. Patients and methods: The study included 120 patients with clinically T1-3N0 OSCC,who were treated primarily with surgery, between January 1, 2006 and December 31, 2010. Immunohistochemistry and semiquantitative analyses were performed in order to determine the level of Hedgehog molecules in OSCC, thus correlating it with clinical and histological prognostic parameters, disease recurrence and survival. Results: There were 99 (82.5 %) males and 21 (17.5 %) females, with an average age of 59 years. Five-year overal survival rate for the whole cohort was 85 %. Eighteen patients has died during the follow-up, while 102 patients were censored. Five-year disease free survival was 53.33 %. Fifty patients had reccurence during follow-up. SHH was expressed in 116 (96.7 %) patients, PTCH in 104 (86.7 %), SMO in 103 (85.8 %), GLI1 in 72 (60 %) patients. We found no correlation of HH molecules expression and clinical or histological prognostic parameters. Also, there was no correlation with DFS and OS except for SHH, whose expression was a statistical relevant factor in accordance to OS (c2=6.74, P=0.034). Conclusions: Accordingly, routine analysis of Hedgehog signaling molecules expression for predicting the biological behaviour of OSCC is not justified. Reccurence, distant metastases, occult metastases and extranodal extension for positive lymph nodes are factors that had an impact on the prognosis and outcome, OS and DFS.