Determination of p53-mediated transactivational ability in radiation-treated cervical cancer.

Abstract

To establish a new predictor of human cervical cancer radioresponse, we investigated the transactivational ability of p53 gene in tumor tissue for use as a marker of both pretreatment and postirradiation levels of mRNA of its downstream gene, WAF1. A total of 38 wild-type p53-bearing patients with histologically proved uterine cervical cancer were treated with definitive radiotherapy. Their p53 status was investigated using a single-strand conformation polymorphism analysis, and human papilloma virus 16, 18, 33, and 58 E6 was determined by polymerase chain reaction in pretreatment biopsy specimens. WAF1 mRNA was estimated by reverse transcriptase-polymerase chain reaction in both pretreatment specimens and those obtained after the administration of 10.8 Gy. Undetectable or low pretreatment levels of WAF1 mRNA were associated with complete response in the majority of cases, whereas only a few patients with a high pretreatment WAF1 level responded to treatment (P = .03). The increase in the postirradiation level of WAF1 mRNA positively correlated with better treatment response and long survival (P = .02). Although the human papilloma virus infection did not change the radiation response directly, it decreased the inducibility of WAF1. Consequently, the lower inducibility of WAF1 resulted in a poor treatment response. This is the first clinical report showing that the transactivational ability of p53 may be a determinant of the efficacy of cervical cancer radiotherapy.