TUMOR ANGIOGENESIS AND P53 MUTATIONS - PROGNOSIS IN HEAD AND NECK-CANCER

Objectives: To assess how p53 gene mutations and microvessel density ( MVD) may be used as prognostic markers for the study and management of head and neck squamous cell carcinomas and to investigate putative as sociations between p53 gene mutations and MVD and the relationship of these factors to tumor response to radiotherapy and/or chemotherapy at 6 weeks. Patients and Design: Thirty-nine patients with squamous cell carcinoma of the head and neck, stages I to IV, who were examined at Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill, and its affi liated hospitals between 1993 and 1995 were monitored. Mutations in th e p53 gene were identified by microdissection of tumor cells on frozen sections, followed by single-strand conformation polymorphism analysi s of the products of polymerase chain reaction amplification of exons 5 to 9. The microvessels were immunostained with monoclonal antibodies to factor VIII and/or CD31. Microvessel counts were done by 2 investi gators blinded to each other's counts and to the p53 gene status. Intr atumoral or peritumoral microvascular ''hot spots'' were assessed and counts were done with an ocular grid in 3 X 200 fields of hot spots by each investigator. The mean of the highest values was considered. Sta tistical analysis was done with the Wilcoxon rank sum test, the log-ra nk test, and proportional hazard models. Results: Of the 39 patients, 13 had mutations in exons 5 to 9. Mutations in the p53 gene were assoc iated with unfavorable overall (P=.003) and disease-free (P=.02) survi val. A strong inverse relationship was seen between MVD and p53 mutati ons (P=.01). No statistically significant relationship was seen betwee n mean MVD and overall and disease-free survival. The response to ther apy differed significantly (P=.03) by p53 mutations, whereas there was no statistical significance with MVD counts. Conclusion: In this stud y a strong inverse relationship was seen between MVD and p53 mutations . p53 Mutations in exons 5 through 9 were associated with unfavorable survival, whereas MVD showed no association with survival.