RESUMO
PURPOSE: Thiamine-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the pentose phosphate pathway transketolases (TKTs), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate dehydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are crucial factors for tumor metabolism. The expression of these enzymes has not been analyzed for carcinogenesis of oral squamous cell carcinoma (OSCC) with special focus on new targeted metabolic therapies as yet. METHODS: TDEs PDH, KGDH (OGDH), and BCKDH were analyzed in normal oral mucosa (n = 14), oral precursor lesions (simple hyperplasia, n = 21; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 46) by immunohistochemistry and western blot (WB) analysis in OSCC tumor cell lines. RESULTS: Although the total numbers of PDH and KGDH (OGDH) positive samples decreased in OSCC, both enzymes were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue. BCKDH has been demonstrated to be significantly overexpressed in the carcinogenesis of OSCC. Specificity of the antibodies was confirmed by WB analysis. CONCLUSIONS: This is the first study showing increased expression of TDEs in OSCC. Metabolic targeting of TDEs (including TKTs) by antagonistic compounds like oxythiamine or oxybenfothiamine may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.
Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Carcinoma de Células Escamosas/enzimologia , Complexo Cetoglutarato Desidrogenase/metabolismo , Neoplasias Bucais/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Tiamina/metabolismo , Western Blotting , Carcinogênese/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Transcetolase/metabolismoRESUMO
BACKGROUND: Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma (OSCC). The purpose of this retrospective study was to review the outcome of patients with oral cavity squamous cell carcinoma treated at a single institution by primary surgical resection with or without adjuvant radiotherapy or radiochemotherapy, or brachytherapy and to identify the factors affecting survival and locoregional control. MATERIALS AND METHODS: We retrospectively reviewed the records of 429 consecutive patients after primary radical R0 tumor resection and 55 patients after brachytherapy in our department between 1997 and 2010. OSCC pathological parameters were analyzed including age, gender, site distribution, tumor size, lymph node involvement, grading, microvascular invasion, lymphatic vessel involvement, and distant metastasis. Descriptive statistics were calculated for each variable and survival was calculated using the univariate Kaplan-Meier method. Prognostic factors were analyzed using the multivariate Cox proportional hazard model. RESULTS: Average tumor size was 10.9 mm (95 % CI for the mean 9.6-12.3). Disease-free survival at 5 years was 65 % and overall 5-year survival was 62 %. On univariate analysis, patients with increased tumor size, lymph node involvement, microvascular invasion, and lymphatic vessel involvement had a significant poor prognosis. Multivariate analysis showed that independent prognostic factors were increased tumor size and microvascular invasion. CONCLUSION: This hospital-based retrospective cohort study points out different clinicopathological prognostic factors of survival in a large patient cohort treated for OSCC. It highlights increased tumor size and microvascular invasion as the most independent prognostic factors in predicting survival in patients with OSCC.