p53 mutations predict non-small cell lung carcinoma response to radiotherapy

In vitro and animal studies, the effect of loss of p53 function on radiosen sitivity is controversial. p21(Waf1/Cip1) is a potent inhibitor of cyclin-d ependent kinases and p21 gene polymorphisms are associated with some human cancers. We sought to determine whether p53 mutations or p21 polymorphisms affect response to radiotherapy in patients with recurrent non-small cell l ung carcinoma (NSCLC). Thirty-four patients with NSCLC who underwent radiot herapy for recurrent tumors after potentially curative resection were studi ed. Gene alterations or polymorphisms were analyzed in DNA from the primary tumor tissue, and the response to radiotherapy was based on the metastatic lesion. Mutations in exons 5-8 of the p53 gene were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analys is, p21 gene polymorphisms were identified by restriction digestion (BsmAI or PstI) of PCR products. Mutations in p53 were found in 13 of 34 pat6ients (38.2%). The response rates (complete plus partial) were 15.4% for patient s with tumors having p53 mutations and 61.9% for patients with wild-type p5 3 (P = 0.013). There was no significant difference between p21 polymorphism s and response to radiation. p53 gene mutations predict response to radioth erapy in NSCLC. Our results provide clinical support for the in vitro model that loss of p53 function decreases radiosensitivity. (C) 1999 Elsevier Sc ience Ireland Ltd. All rights reserved.