Wilson CR, Davidson SE, Margison GP, Jackson SP, Hendry JH and West CML. (2000). Expression of Ku70 correlates with survival in carcinoma of the cervix. British Journal of Cancer 83:1702-1706.
Cervical carcinoma affects around 3400 women in the UK each year and advanced
disease is routinely treated with radiation. As part of a programme to establish
rapid and convenient methods of predicting tumour and patient responses
to radiotherapy, we have examined the relationship between the pre-treatment
expression of the Ku components of the DNA damage recognition complex DNA-PK
and patient survival in cervical carcinoma. Using immunohistochemistry of
formalin-fixed sections of tumour biopsies, antibodies to Ku70 and Ku80
stained identical regions of tumour and there was a high degree of correlation
between the mean number of cells stained positive for the two components
in 77 tumours (r =0.82, P< 0.001). In 53 tumours there was a borderline
significant correlation between measurements of tumour radiosensitivity
(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 tumours with
a low number of Ku70 or Ku80 positive cells were radiosensitive. Furthermore,
using log-rank analysis there was significantly higher survival in the patients
whose tumours had a low Ku70 expression (P =0.046). This difference was
also reflected with Ku80, but did not reach statistical significance (P
= 0.087). The study suggests that lack of Ku protein leads to radiosensitivity
in some tumours and that other factors are responsible for radiosensitive
tumours with high Ku expression. It is likely that the most accurate prediction
of treatment outcome will lie in assessing the expression of several proteins
involved in the recognition and repair of DNA damage, one of which will
be Ku.