Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma

摘要

OBJECTIVE: To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS). Animals-27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or gamma radiation. PROCEDURES: Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated. RESULTS: Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at & or = 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE: p53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.