Expression of Ku70 correlates with survival in carcinoma of the cervix

Cervical carcinoma affects around 3400 women in the UK each year and advanc ed disease is routinely treated with radiation. As part of a programme to e stablish rapid and convenient methods of predicting tumour and patient resp onses to radiotherapy, we have examined the relationship between the pre-tr eatment expression of the Ku components of the DNA damage recognition compl ex DNA-PK and patient survival in cervical carcinoma. Using immunohistochem istry of formalin-fixed sections of tumour biopsies, antibodies to Ku70 and Ku80 stained identical regions of tumour and there was a high degree of co rrelation between the mean number of cells stained positive far the two com ponents in 77 tumours (r = 0.82, P < 0.001). In 53 tumours there was a bord erline significant correlation between measurements of tumour radiosensitiv ity (surviving fraction at 2 gray: SF2) and Ku70 expression (r = 0.26, P = 0.057) and no correlation for Ku80 (r = 0.18, P = 0.19). However, all tumou rs with a low number of Ku70 or Ku80 positive cells were radiosensitive. Fu rthermore, using log-rank analysis there was significantly higher survival in the patients whose tumours had a low Ku70 expression (P = 0.046). This d ifference was also reflected with Ku80, but did not reach statistical signi ficance (P = 0.087). The study suggests that lack of Ku protein leads to ra diosensitivity in some tumours and that other factors are responsible for r adiosensitive tumours with high Ku expression. It is likely that the most a ccurate prediction of treatment outcome will lie in assessing the expressio n of several proteins involved in the recognition and repair of DNA damage, one of which will be Ku. (C) 2000 Cancer Research Campaign.