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The nuclear phosphoprotein p53 is important in protecting the genome. p53 protein expression and phosphorylation status is upregulated following DNA damage and can induce growth arrest, DNA repair, apoptosis, and cell senescence. p53 is frequently overexpressed in tumors and is mutated in many human cancers. In head and neck squamous cell carcinoma (HNSCC), p53 is mutated in 40% to 60% of cases. Such alterations of the p53 gene can result in cellular accumulation of mutant and wild-type p53 protein. Several laboratories have reported that antibodies to p53 are present in cancer patient sera and that the antibodies may be useful in detecting malignant tumors in patients with head and neck cancer. A previous study of 80 HNSCC patients, reported that p53 antibody was present in 18.7% of pretreatment sera and was associated with increased risk of cancer death. To evaluate the relationship between the presence of antibody and response to treatment we studied antibodies in the sera of 45 HNSCC patients, using the ELISA method developed Thierry Soussi. Sera are screened in duplicate at two dilutions on plates coated on one half with protein extracts from Sf9 cells and on the other half with protein extracts from Sf9 cells expressing human p53. To assess the reliability of the test all sera from ten patients were retested in a separate experiment and all results were confirmed. All patients were treated in the Department of Otolaryngology/Head and Neck Surgery at the University of Turku, Finland. A ratio of the absorbance value on the p53 containing wells, to that of the control Sf9 protein greater than 1.5 was used as a positive result. Pretreatment sera were available from 41 of the 45 patients. Of these, 11 of 41 (27%) patients had p53 antibody prior to initial treatment with radiation or surgery. Nine of these patients had a decrease in p53 antibody titer after initial treatment. The two patients, whose p53 antibody levels increased after initial treatment, experienced recurrence, one died of disease and the other remained NED. Three of the 9 patients whose p53 antibody levels decreased, had recurrence, and one of those was still positive for p53 antibodies. Overall, 10 of 45 patients had p53 antibody after initial treatment; and of these 50% (5 of 10) experienced recurrence. Thus, antibodies against p53 can be used to monitor patients before and after treatment for residual or recurrent disease. Serum p53 antibody status may be useful to identify patients in need of close monitoring and possibly more aggressive treatment to prevent recurrence and death. Acknowledgement: This research is supported in part by the NIH NCI through the University of Michigan’s Cancer Center Support Grant (5 P30 CA46592) and grant (1 R01 CA83087); an NIH NIDCR grant (1 R01 DE13346); the NIH through the University of Michigan’s Head and Neck SPORE grant (1 P50 CA97248); and the Research Center Core grant NIH NIDCD (P30 DC05188).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]