Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

BMC Cancer

Research Article

Elizabeth Kornaga¹  Stephanie K Petrillo¹  Alexander C Klimowicz¹  Pinaki Bose¹  Anthony M Magliocco²  Nigel T Brockton³  Shamir Chandarana⁴  T Wayne Matthews⁴  Joseph C Dort⁴ 

[1] Department of Oncology, University of Calgary, Calgary, Canada;Department of Oncology, University of Calgary, Calgary, Canada;H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, 33612, Tampa, FL, USA;Department of Population Health Research, Alberta Health Services – Cancer Care, Calgary, Canada;Division of Otolaryngology-Head and Neck Surgery, University of Calgary, Calgary, Canada;

关键词: AQUA;    Bax;    Bcl-2;    Bcl-XL;    Oral cancer;    prognosis;   

DOI  :  10.1186/1471-2407-12-332

 received in 2012-04-25, accepted in 2012-07-27,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundResistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique.MethodsSixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model.ResultsBax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013].ConclusionsThe AQUA technique used in our study eliminates observer bias and provides reliable and reproducible estimates for biomarker expression. AQUA also provides essential measures of quality control that cannot be achieved with manual biomarker scoring techniques. Our results support the use of Bax protein expression as a prognostic marker in conjunction with other clinico-pathological variables when designing personalized treatment strategies for OSCC patients.

【 授权许可】

Unknown   
© Bose et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.