Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy.

Abstract

To investigate the association between the cancer cell proliferation fraction and the risk of recurrence in laryngeal cancer patients treated without systemic therapy. Paraffin-embedded tumor samples from 90 laryngeal cancer patients were stained for cyclin A and the Ki-67 antigen by immunohistochemistry. The patients were treated with partial or total laryngectomy followed by postoperative radiotherapy to a total dose of 50 Gy or greater. The median follow-up time was 91 months (minimum 48 months). High cyclin A expression (>19% positive cancer cell nuclei, the highest tertile) was associated with a high rate of locoregional tumor recurrence and unfavorable disease-free and overall survival as compared with cases with a lower expression (p = 0.025, 0.032, and 0.042, respectively). In a multivariate analysis, high cyclin A expression was an independent predictor of poor disease-free survival (RR 2.4, 95% CI 1.2-4.9, p = 0.013) and overall survival (RR 2.1, 1.2-3.6, p = 0.012), together with a poor Karnofsky's performance status and the presence of positive margins at surgery. Ki-67 expression was not an independent predictor of survival, but cancers with high Ki-67 expression (>34% nuclei positive, the highest tertile) recurred more frequently locoregionally when treated with split-course radiotherapy than when treated with a continuous course of therapy (p = 0.035), whereas the presence of a planned split did not influence the frequency of locoregional recurrences when Ki-67 expression was lower (p = 0.93). Cancer cell cyclin A expression is a novel predictive factor for outcome in laryngeal cancer treated with surgery and postoperative radiotherapy. Planned gaps in the radiotherapy course are deleterious in patients with a high proliferative fraction, and immunostaining for the Ki-67 antigen may be useful in identification of such patients.