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

Abstract

Purpose: To investigate the association between the cancer cell proliferation fraction and the risk of recurrence in laryngeal cancer patients treated without systemic therapy.

Methods and materials: 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).

Results: 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).

Conclusion: 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.