Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy

A relationship between hypoxia and apoptosis has been identified in vitro a nd in experimental tumours. The aim of this study was to investigate the re lationship between apoptosis, hypoxia and the change in oxygenation during radiotherapy in human squamous cell carcinoma of the cervix. Forty-two pati ents with locally advanced disease underwent pretreatment evaluation of tum our oxygenation using an Eppendorf computerized microneedle electrode. Twen ty-two of these patients also had a second evaluation of tumour oxygenation after receiving 40-45 Gy external beam radiotherapy. Paraffin-embedded his tological sections were obtained from random pretreatment biopsies for all 42 patients. Apoptotic index (Al) was quantified by morphology on TUNEL sta ined sections. No correlation was found between pretreatment measures of Al and either the median pO(2) (r= 0.12, P = 0.44) or percentage of values < 5 mmHg (r = -0.02, P = 0.89). A significant positive correlation was found between Al and the change in tumour oxygenation (ratio of pre:post-treatmen t % values < 5 mmHg) following radiotherapy (r = 0.61, P = 0.002), The lack of correlation between apoptosis and hypoxia may occur because the Eppendo rf measures both acute and chronic hypoxia, and the relative ability of acu te hypoxia to induce apoptosis is unknown. These results indicate that cell death via apoptosis may be a mechanism of tumour reoxygenation during radi otherapy. (C) 2000 Cancer Research Campaign.