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, aggr essiveness, 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 o f the head and neck were included in the study. The expression of p53, Bcl- 2, Mcl-1, Bar, and Bak was assessed by immunohistochemical analysis. The te rminal deoxytransferase-mediated deoxyuridine nick end-labeling assay was u sed to quantify apoptosis by flow cytometry. Results: Tumor cells containing immunostaining for the antiapoptotic protei ns Bcl-2 and Mcl-1 were present in 4 (15%) and 24 (92%) of the cases evalua ted, respectively, whereas immunopositivity for the proapoptotic proteins B ar and Bak was found in 9 (35%) and 24 (92%) of the samples. Immunoreactivi ty to p53 was detected in 20 (77%) of the samples. There was a positive cor relation between the expression of Bcl-2 and Bar and between Mcl-1 and Bak. A low fraction of apoptotic cells (<2.5%) in the pretreatment tumor sample s was significantly correlated with increased 2-year survival in these pati ents. Conclusions: Our results establish the frequent expression of the Bcl-2 fam ily proteins Bcl-2, Mcl-1, Bar, and Bak ire locally advanced head and neck cancer. In addition, this study suggests that the apoptotic fraction in pre treatment tumor samples might be of prognostic importance for the outcome i n these patients.