Prognostička vrijednost izraženosti koštanoga morfogenetskoga proteina 6 u planocelularnim karcinomima usne šupljine [Prognostic significance of bone morphogenetic protein 6 (BMP6) expression in oral squamous cell carcinoma]

Suton, Petar (2016) Prognostička vrijednost izraženosti koštanoga morfogenetskoga proteina 6 u planocelularnim karcinomima usne šupljine [Prognostic significance of bone morphogenetic protein 6 (BMP6) expression in oral squamous cell carcinoma]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Bone morphogenetic proteins, BMPs, are growth and differentiation factors, originally isolated as molecules which in vivo stimulate ectopic bone and cartilage formation. Overexpression of BMP6 has been shown in various malignant tumors. However, the prognostic significance of its expression in oral squamous cell carcinoma (OSCC) is still unknown. Immunohistochemistry and semiquantitative analyses were performed in order to determine the level of BMP6 in OSCC, thus correlating it with clinical and histological prognostic parameters, disease recurrence and survival. Patients and methods: The study included 120 patients with clinically T1-3N0 OSCC,who were treated primary surgically, between January 1, 2003 and December 31, 2008. Results: There were 99 (82,5%) males and 21 (17,5%) females, with an average age of 59 years. Five-year disease-specific survival rate for the whole cohort was 79,4%. Twenty patients had died during the follow-up, while 100 patients were censored. Patients with tumors smaller than 2,1 cm determined histologically showed higher incidence of strong BMP6 expression. No statistically significant corellation was detected between the level of BMP6 expression and other clinico-pathological factors. Similarly, the expression of BMP6 was neither associated with disease recurrence nor was it associated with patient's survival. Conclusions: Accordingly, routine analysis of BMP6 expression for predicting the biological behaviour of OSCC is not justified. The level of BMP6 expression cannot be considered as a prognostic factor in OSCC. In multivarite model, positive surgical margin, moderate tumor cell differentiation and metastatic cervical lymph nodes located at levels 4 and/or 5 were independent predictors of survival.

Abstract in Croatian

Uvod: Koštani morfogenetski proteini (BMP, od eng. bone morphogenetic proteins) su čimbenici rasta i diferencijacije koji su prvotno izolirani iz kosti, kao molekule koje potiču ektopično stvaranje kosti i hrskavice in vivo. Iako je BMP6 pojačano izražen u različitim zloćudnim tumorima, nije poznata prognostička vrijednost njegove izraženosti u planocelularnom karcinomu usne šupljine. Ovim su istraživanjem metode imunohistokemije i semikvantitativne analize upotrijebljene za određivanje izraženost BMP6 u planocelularnom karcinomu usne šupljine. Dobiveni rezultati su korelirani s kliničkim i histološkim prognostičkim parametrima, pojavom recidiva bolesti i preživljenjem bolesnika. 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 2003. do 31. prosinca 2008. godine. Rezultati: Ispitivana skupina brojila je 99 (82,5%) muškaraca i 21 (17,5%) ženu, prosječne dobi 59 godina. Prosječno petogodišnje preživljenje bilo je 79,4%. Tijekom praćenja je od osnovne bolesti umrlo 20 bolesnika, a 100 ih je cenzurirano. BMP6 je bio izražen u 109 (90,8%) tumora. Bolesnici s tumorima histološkog promjera do 2,1 cm imali su statistički značajno češće prisutan snažan izražaj BMP6. Stupanj izraženost proteina BMP6 nije bio povezan s drugim kliničkim ili histološkim čimbenicima. Jednako tako, izraženost BMP6 nije povezana s pojavom recidiva bolesti, i nije povezana s duljinom preživljenja. Zaključci: S obzirom na to da jačina izraženosti BMP6 ne ovisi o biološkom ponašanju tumora, rutinsko određivanje njegove izraženosti u karcinomu usne šupljine, metodom imunohistokemije, nije opravdano. Među pokazateljima kojima je dokazana multivarijatna povezanost s preživljenjem, statistički značajne i međusobno nezavisne značajke su umjerna zrelost tumora, pozitivan rub resekcije te zahvaćenost područja vrata 4 i/ili 5.

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