Clinical Research Papers:
Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients
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Andreas Knopf1, Justine Lempart1, Murat Bas1, Julia Slotta-Huspenina2, Naglaa Mansour1, Marie Kristin Fritsche1
1Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany
2Technische Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, 81675 München, Germany
Andreas Knopf, e-mail: [email protected]
Keywords: Tongue, oncogenes, tumour suppressor genes, oral cancer, young patients
Received: October 23, 2014 Accepted: December 03, 2014 Published: January 30, 2015
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.
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