Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients

Abstract

// Andreas Knopf 1 , Justine Lempart 1 , Murat Bas 1 , Julia Slotta-Huspenina 2 , Naglaa Mansour 1 , Marie Kristin Fritsche 1 1 Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany 2 Technische Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, 81675 München, Germany Correspondence to: Andreas Knopf, e-mail: a.knopf@lrz.tum.de Keywords: Tongue, oncogenes, tumour suppressor genes, oral cancer, young patients Received: October 23, 2014      Accepted: December 03, 2014      Published: January 30, 2015 ABSTRACT Objectives : The occurrence of squamous cell carcinoma of the tongue (SCCT) of young patients increased. There are still controversies about patient prognosis. The underlying molecular mechanisms remain unclear. Methods : 276 patients (66 ≤45, 210 >45 years) with SCCT were included. Clinical parameters and survival data were assessed. Oncogenes and tumor suppressors were analyzed via immunohistochemistry (p53, CXCR4, p16, EGFR) and qPCR ( CDK4, CDKN2A, TP53, MDM2, AKT1, PIK3CA, NRAS, HRAS, KRAS, HGF, MET, EGF, ATM, BRCA1, E2F1, FHIT, RUNX3, STK11, BCL2, CTNNB1 ). Results : The median overall survival was 142 (≤45 years) and 34 months (>45 years) ( p < 0.0001; HR [95%CI]: 0.37 [0.30–0.58]). Disease specific survival in patients ≤45 years was with 181 months significantly higher than in patients >45 years ( p < 0.0001; HR [95%CI]: 0.33 [0.26–0.57]). Immunhistochemistry visualized a comparable expression of analyzed proteins. QPCR demonstrated in patients ≤45 years a higher expression of genes that are associated with carcinogenesis ( CTNNB1, STK11, CDKN2A, HGF, MET ) as well as tumor suppressors that constitute an enhanced radio-sensitivity ( ATM, BRCA1E2F1, FHIT ). Conclusion : Derogation of the WNT-CTNNB1-STK11 and CDKN2A-HGF-MET pathway can constitute the carcinogenesis, while the higher expression of radio-sensitizers ATM, BRCA1E2F1 and FHIT can explain the better OS/DSS in young patients.