The prognostic significance of proliferative activity, apoptosis and expression of DNA topoisomerase II alpha in multimodally-treated oesophageal squamous cell carcinoma.

The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy +/- surgical resection) and the parameters proliferative activity, apoptotic index and expression of the nuclear enzyme topoisomerase II alpha (topo II alpha) in pre-therapeutic tumour biopsies. Fifty-eight patients who took part in a prospective multicentred trial received radiochemotherapy, optionally followed by surgery. Pre-therapeutic biopsies were immunohistochemically investigated for the extent of proliferation (MIB-I index) and expression of the topo II alpha-enzyme. The apoptotic index was determined by the TUNEL-assay. The three parameters were correlated with tumour response to polychemotherapy and with overall survival. Topo II alpha expression was found in all samples with different percentages of positive cells. The proliferation indices ranged between 9% and 97% (median: 43%) while the apoptotic indices ranged between 0.2% and 2.8% (median: 0.5%). Strong expression of topo II alpha (>50% positive tumour cells) was positively-correlated with response to polychemotherapy (p=0.016) whereas proliferative activity or apoptotic index showed no impact. None of the three parameters under investigation was predictive of overall survival. Pre-therapeutic determination of topo II alpha expression may predict chemosensitivity of oesophageal squamous cell carcinomas. However, determination of proliferative activity and apoptotic index has no predictive value.