Spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced head and neck cancer

Background: Apoptotic cell death plays a key role in the pathogenesis, aggressiveness, and therapy responsiveness of cancer. The suicidal machinery of apoptosis is genetically controlled. Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. Objective:To assess the rate of spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced squamous cell carcinomas of the head and neck. Design: Twenty-six patients with locally advanced squamous cell carcinoma of the head and neck were included in the study. The expression of p53, Bcl-2, Mcl-1, Bax, and Bak was assessed by immunohistochemical analysis. The terminal deoxytransferase-mediated deoxyuridine nick end-labeling assay was used to quantify apoptosis by flow cytometry. Results: Tumor cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 4 (15%) and 24 (92%) of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 9 (35%) and 24 (92%) of the samples. Immunoreactivity to p53 was detected in 20 (77%) of the samples. There was a positive correlation between the expression of Bcl-2 and Bax and between Mcl-1 and Bak. A low fraction of apoptotic cells (<2.5%) in the pretreatment tumor samples was significantly correlated with increased 2-year survival in these patients. Conclusions: Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax, and Bak ire locally advanced head and neck cancer. In addition, this study suggests that the apoptotic fraction in pretreatment tumor samples might be of prognostic importance for the outcome in these patients.