Bcl-2 blocks cisplatin-induced apoptosis and predicts poor outcome following chemoradiation treatment in advanced oropharyngeal squamous cell carcinoma

William A. Michaud, Anthony C. Nichols, Edmund A. Mroz, William C. Faquin, John R. Clark, Shahnaz Begum, William H. Westra, Hiroshi Wada, Paul M. Busse, Leif W. Ellisen, James W. Rocco

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Abstract

Purpose: This study aimed to test the hypothesis that elevated expression of antiapoptotic Bcl-2 family proteins predicts a poor therapeutic response of oropharyngeal squamous cell carcinoma (OPSCC) to concurrent platinum-based chemoradiation therapy. Experimental Design: Levels of Bcl-2, Bcl-X L, and Bcl-w were determined and correlated with resistance to cisplatin in a large panel of cell lines derived from squamous cell carcinoma of the head and neck(HNSCC). Univariate and multivariate analyses were used to evaluate the relationship between Bcl-2 and Bcl-X L expression and disease-free survival following chemoradiation therapy in a uniformly treated cohort of patients with OPSCC. Results: In HNSCC cell lines, high endogenous Bcl-2 expression was associated with increased cisplatin resistance, and experimental overexpression of Bcl-2 promoted cisplatin resistance. In patients, tumors positive for Bcl-2 before treatment had greater riskof treatment failure (hazard ratio, 5.99; 95% confidence interval, 1.73-20.8; P = 0.0014). In contrast, endogenous Bcl-X L showed no correlation either with cisplatin sensitivity in the cell line panel in vitro, or with risk of recurrence in vivo (hazard ratio, 1.28; 95% confidence interval, 0.39-4.19; P = 0.68). Associations between Bcl-2 expression and other clinical characteristics did not account for the predictive value of Bcl-2. Conclusions: Immunohistochemical assessment of Bcl-2 in pretreatment biopsy specimens can predict response of advanced OPSCC to concurrent platinum-based chemoradiation. As treatments targeting Bcl-2 and its family members become available, this immunohistochemical assessment could help personalize therapy by identifying a subpopulation of patients with a poor prognosis who might benefit from such treatments.

Original languageEnglish (US)
Pages (from-to)1645-1654
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number5
DOIs
StatePublished - Mar 1 2009

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Michaud, W. A., Nichols, A. C., Mroz, E. A., Faquin, W. C., Clark, J. R., Begum, S., Westra, W. H., Wada, H., Busse, P. M., Ellisen, L. W., & Rocco, J. W. (2009). Bcl-2 blocks cisplatin-induced apoptosis and predicts poor outcome following chemoradiation treatment in advanced oropharyngeal squamous cell carcinoma. Clinical Cancer Research, 15(5), 1645-1654. https://doi.org/10.1158/1078-0432.CCR-08-2581