APOPTOSIS, INTRINSIC RADIOSENSITIVITY AND PREDICTION OF RADIOTHERAPY RESPONSE IN CERVICAL-CARCINOMA

Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the perce ntage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsi es. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-t herapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were al so recorded as markers for proliferation. Patients were divided into t hose with an AI above or below the median and in general increasing ap optosis was associated with poor prognosis. The 5-year survival rate f or tumours with an AI below the median was 79% and was significantly g reater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurre nce-free rate for patients with an AI below the median compared with t hose with an AI above the median (79 versus 61%, p = 0.012), In additi on, AI and SF2 acted as independent prognostic indicators. Patients wi th both an SF2 and AI value above the median did badly (25% 5-year sur vival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showe d correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0,25,p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apopto sis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients, The study raises the possibility of AI and SF2 bei ng used together as predictors of tumour response to radiotherapy.