Micronucleus assay in vivo provides significant prognostic information in human cervical carcinoma; the updated analysis

Abstract

Purpose : Reanalysis after a 5-year follow-up previously presented relationships between spontaneous and radiation-induced micronucleus frequencies in tumour cells and the clinical outcome of patients with advanced stages (II B-IV B) of cervix carcinomas treated with radiotherapy. Materials and methods : Spontaneous and induced in vitro and in vivo micronucleus frequencies were determined and related to clinical parameters. Data were analysed by the univariate Kaplan-Meier method and multivariate Cox proportional hazards model. Results : In univariate analysis stage, spontaneous micronucleus frequency before radiotherapy (MNSP) and per cent increment of micronucleus level in vivo after 20 Gy in relation to spontaneous pretreatment level were statistically significant predictors of 5-year recurrence-free, disease-free and overall survival. Neither micronucleus frequency (MN/BNC at 2 Gy) nor proliferating fraction (%BNC at 0 Gy) estimated in vitro (in primary culture) were related to radiotherapy outcome. The age of patients was not associated with clinical results. Multivariate analysis demonstrated that the clinical stage of disease, the high frequency of spontaneous micronuclei and low-induced micronucleus frequency were independent and significantly unfavourable predictive factors for disease-free and overall survival. But for local control, only high MNSP and low-induced MN frequency were significant negative predictive variables. Conclusions : A high frequency of micronuclei before radiotherapy and a slight increase of micronucleus frequency during radiotherapy measured after 10 fractions of 2 Gy were independent on stage, statistically significant adverse predictors of clinical outcome in cervical carcinoma patients treated with radiotherapy.