The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer

Background: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major fun ction of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of pati ents with advanced non-small cell lung cancer and induction treatment. Meth ods: Patients with complete or partial remission were compared with those w ith stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequ encing (exons 2-11), Results: A normal TP53 genotype proved to be significa ntly associated with major response to chemotherapy (P < .001), Overall, no association was found between p53 protein expression and TP53 genotype, A normal TP53 genotype was found to be highly sensitive in predicting respons e to treatment, whereas a mutant genotype was revealed to be specific in pr edicting lack of response. The difference in overall length of survival tva s significant between patients exhibiting a normal TP53 genotype (correspon ding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P = .027). Conclusions: In a small cohort of patients with ad vanced non-small cell lung cancer we found a direct link between normal TP5 3 genotype and response to cisplatin-based induction treatment and also bet ween mutant genotype and resistance to treatment, whereas p53 immunohistoch emical result was predictive of neither.