p53 alterations predict tumor response to neoadjuvant chemotherapy in headand neck squamous cell carcinoma: A prospective series

Purpose: The tumor suppressor gene p53 ploys a crucial role in cell cycle c ontrol and apoptosis in response to DNA damages. p53 gene mutations and all elic losses at 17p are one of the most common genetic alterations in primar y head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gen e have been shown to contribute to carcinogenesis and drug resistance. Patients and Methods: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status wa s characterized in 106 patients with HNSCC (p53 mutations, allelic losses a t p53 locus, and plasma anti-p53 antibodies) ta determine the existence of a relationship between p53 gene status and response to neoadjuvant chemothe rapy. Results: Exons 4 to 9 of the p53 gene were analyzed, and mutations were fou nd in 72 of 106 patients with HNSCC. p53 mutations were associated with los s of heterozygosity at chromosome 17p (P < .001). The prevalence of p53-mut ated tumors was higher in the group of patients with nonresponse to neoadju vant chemotherapy than in the group of responders (81% v 61%, respectively; P < .04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was signifi cant (87% v 57%, respectively: P = .003), A multivariate analysis showed th at p53 status is an independent predictive factor of response to chemothera py. Conclusion: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC. (C) 2000 by Am erican Society of Clinical Oncology.