Ki-S1--a prognostic marker for hypopharyngeal carcinoma with potential predictive value for response to chemotherapy

It has previously been shown that the proliferative activity, determined by means of the monoclonal antibody Ki-S11 against the Ki-67 protein, is a significant prognostic factor for squamous cell carcinoma of the hypopharynx (SCCH). We now investigated the prognostic and the predictive impact of Ki-S1, a monoclonal antibody which detects an epitope of topoisomerase II alpha, another proliferation-associated antigen.

The proliferation index (PI) in terms of Ki-S1 immunolabeling was evaluated on tumor specimens from 131 patients with SCCH. Survival probabilities over an observation time of 72 months were calculated by Kaplan-Meier analysis.

Patients with low PI (< or = 45%) had a significantly improved 5-year survival (33.2%) compared with patients with high PI (> 45%), of whom only 11% survived after 5 years (p = 0.001). Since there was no significant difference between the results obtained with Ki-S1 and Ki-S11, the present data confirm the prognostic significance of the proliferative activity in SCCH.

Topoisomerase II alpha is also the target of many antineoplastic drugs and it has been proposed that its expression in tumor cells correlates with chemosensitivity. The high average topoisomerase II alpha content in SCCH therefore promises a good responsiveness to topoisomerase inhibitors. Because Ki-S1 directly measures cellular topoisomerase II alpha expression, it might be exploited not only as a prognostic indicator but also as a predictive marker for patients with SCCH.