Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy

BACKGROUND: Radiotherapy is used in the treatment of laryngeal carcinoma. The search for biologic parameters that could be used to identify patients who will respond to radiotherapy is crucial. The aim of this study was to determine whether the Ki-67 and p53 indices and the pretreatment apoptotic index would be useful in predicting local control and survival for a group of laryngeal carcinoma patients given postoperative radiotherapy. METHODS: Fifty-seven patients with laryngeal carcinoma treated between 1988 and 1993 were included in this study. Postoperative radiotherapy was given to a mean dose of 57.7 gray (Gy) (range, 50-68; median, 60) in 2-Gy daily fractions. Ki-67 and p53 immunostaining were performed on paraffin-embedded tissue. Cells were evaluated for apoptosis using hematoxylin and eosin-stained slides. Clinicopathologic tumor characteristics were studied in relation to Ki-67, p53, and apoptotic indices, and as prognostic factors for local control and survival in both univariate and multivariate analysis. RESULTS: The Ki-67, p53, and pretreatment apoptotic indices were not related to any clinicopathologic tumor characteristics. Five-year actuarial local control for the whole group was 47%. Patients with tumors that had low Ki-67 proliferation had better long term local control (P < 0.01). and survival (P < 0.03). p53 expression was not predictive of local control or survival in this study. Patients with tumors that had low pretreatment apoptotic indices had better local control (P < 0.049) and survival (P < 0.056) than patients with highly apoptotic tumors. Tumor extension and the pretreatment apoptotic index were significant predictive factors for local control and survival in multivariate analysis. CONCLUSIONS: Ki-67 proliferation measurement and the pretreatment apoptotic index are useful in predicting the clinical outcome of laryngeal carcinoma patients referred for radiotherapy. The role of p53 oncoprotein determination in predicting these outcomes is unclear. Assessment of biologic tumor characteristics could aid in the selection of patients for different treatment strategies.