Activation of Akt at T308 and S473 in alcohol, tobacco and HPV-induced HNSCC: is there evidence to support a prognostic or diagnostic role?

Experimental Hematology & Oncology

Sarah J Jones²  Lynda Cochrane¹  Michaelina Macluskey²  Ian R Ellis²  Mohammad R Islam² 

[1] Division of Population Health Science, Medical Research Institute, University of Dundee, Dundee DD2 4BF, UK;Division of Oral and Maxillofacial Clinical Sciences, The Dental School, University of Dundee, Dundee DD1 4HR, UK

关键词: Biomarker;    Prognosis;    Risk factors;    HNSCC;    pAkt S473;    pAkt T308;   

Others  :  1135301
DOI  :  10.1186/2162-3619-3-25

 received in 2014-08-11, accepted in 2014-10-07,  发布年份 2014

【 摘 要 】

Background

Tobacco, alcohol and HPV infection are associated with increased risk of HNSCC. However, little is known about the underlying signaling events influencing risk. We aimed to investigate the relationship between these risk factors and Akt phosphorylation, to determine prognostic value.

Method

VEGF-positive HNSCC biopsies, with known HPV status, were analyzed by immunohistochemistry (IHC) for Akt, phosphorylated at residues S473 and T308. Comparisons between the tissues were carried out using a Mann–Whitney U test. Associations between the variables and continuous immunohistochemical parameters were evaluated with general linear models. Patient characteristics and pAkt IHC score were analyzed for possible association with overall survival by Cox proportional hazard models.

Results

Immunohistochemistry revealed that cancer patients had significantly higher levels of pAkt T308 than S473 (P < 0.001). Smoking and alcohol were found to be independent risk factors for Akt phosphorylation at T308 (P = 0.022 and 0.027, respectively). Patients with tumors positive for HPV or pAkt S473 had a poorer prognosis (P = 0.005, and 0.004, respectively). Patients who were heavy drinkers were 49 times more likely to die than non-drinkers (P = 0.003). Patients with low pAkt T308 were more likely to be HPV positive (P = 0.028). Non-drinkers were also found to have lower levels of pAkt T308 and were more likely to have tumors positive for HPV than heavy drinkers (P = 0.044 and 0.007, respectively).

Conclusion

This study suggests different mechanisms of carcinogenesis are initiated by smoking, alcohol and HPV. Our data propose higher phosphorylation of Akt at T308 as a reliable biomarker for smoking and alcohol induced HNSCC progression and higher phosphorylation of Akt at S473 as a prognostic factor for HNSCC.

【 授权许可】

   
2014 Islam et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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