Knopf Andreas, Lempart Justine, Bas Murat, Slotta-Huspenina Julia, Mansour Naglaa, Fritsche Marie Kristin
Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
Technische Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, 81675 München, Germany.
Oncotarget. 2015 Feb 20;6(5):3443-51. doi: 10.18632/oncotarget.2850.
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.
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).
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).
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.
年轻患者舌鳞状细胞癌(SCCT)的发病率有所上升。关于患者预后仍存在争议。其潜在的分子机制尚不清楚。
纳入276例SCCT患者(66例年龄≤45岁,210例年龄>45岁)。评估临床参数和生存数据。通过免疫组织化学(p53、CXCR4、p16、EGFR)和定量聚合酶链反应(qPCR)(CDK4、CDKN2A、TP53、MDM2、AKT1、PIK3CA、NRAS、HRAS、KRAS、HGF、MET、EGF、ATM、BRCA1、E2F1、FHIT、RUNX3、STK11、BCL2、CTNNB1)分析癌基因和肿瘤抑制基因。
总体生存中位数为142个月(年龄≤45岁)和34个月(年龄>45岁)(p<0.0001;风险比[95%置信区间]:0.37[0.30 - 0.58])。年龄≤45岁患者的疾病特异性生存时间为181个月,显著高于年龄>45岁的患者(p<0.0001;风险比[95%置信区间]:0.33[0.26 - 0.57])。免疫组织化学显示所分析蛋白质的表达情况相似。qPCR表明,年龄≤45岁的患者中,与致癌作用相关的基因(CTNNB1、STK11、CDKN2A、HGF、MET)以及构成增强放射敏感性的肿瘤抑制基因(ATM、BRCA1、E2F1、FHIT)表达较高。
WNT - CTNNB1 - STK11和CDKN2A - HGF - MET通路的失调可能构成致癌机制,而放射增敏剂ATM、BRCA1、E2F1和FHIT的高表达可以解释年轻患者更好的总生存期/疾病特异性生存期。