Mutation of p53 Gene and Its Correlation with the Clinical Outcome in Dogs with Lymphoma

Abstract

Background: p53 plays a key role in the apoptotic event induced by chemotherapeutic agents. Mutation of p53 gene has been observed in various spontaneous tumors in humans and is associated with a poor prognosis. p53 abnormalities have been evaluated in several tumors in dogs; however, the association of p53 gene mutation with clinical outcome in dogs with lymphoma has not been documented. Hypothesis/Objectives: The aim of this study was to examine p53 mutation in canine lymphoma cells and its association with the clinical outcome. Animals: Forty-three dogs with previously untreated high-grade lymphoma referred to the University of Tokyo were included in this study. Methods: Prospective cohort study. We examined p53 gene (exon 4-8) mutation in the tumor tissues from 43 dogs with lymphoma using PCR-SSCP (polymerase chain reaction - single-strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. Results: Of the 43 dogs, 7 dogs (16%) had p53 mutation, whereas 36 dogs (84%) were devoid of p53 mutation. Overall response rate after remission induction was significantly lower (33% versus 88%, P =.002) in dogs with lymphomas having p53 mutation than those with lymphomas devoid of p53 mutation. Overall survival time was significantly shorter (67 days versus 264 days, P =.004) in dogs with lymphoma with p53 mutation than those with lymphoma retaining wild-type p53. Conclusion and Clinical Importance: Mutations of p53 gene were detected in a proportion of canine lymphoma cells from untreated dogs and can be associated with a poor prognosis.