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. T he search for biologic parameters that could be used to identify patients w ho will respond to radiotherapy is crucial. The aim of this study was to de termine whether the Ki-67 and p53 indices and the pretreatment apoptotic in dex 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-sta ined slides. Clinicopathologic tumor characteristics were studied in relati on to Ki-67, p53, and apoptotic indices, and as prognostic factors for loca l control and survival in both univariate and multivariate analysis. RESULTS. The Ki-67, p53, and pretreatment apoptotic indices were nor relate d 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 surviva l (P < 0.03). p53 expression was not predictive of local control or surviva l in this study. Patients with tumors that had low pretreatment apoptotic i ndices had better local control (P < 0.049) and survival (P < 0.056) than p atients with highly apoptotic rumors. Tumor extension and the pretreatment apoptotic index were significant predictive factors for local control and s urvival 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 determinat ion in predicting these outcomes is unclear. Assessment of biologic tumor c haracteristics could aid in the selection of patients for different treatme nt strategies. Cancer 1998;83: 2493-501, (C) 1998 American Cancer Society.