Prognostic significance of the expression levels of the p16, p15, and p14 genes in dogs with high-grade lymphoma.

The prognostic significance of the inactivation of the p16, p15, and p14 genes has been reported in lymphoid malignancies in humans. To evaluate the relationship between inactivation of the p16, p15, and p14 genes and prognosis in canine high-grade lymphoma, primary tumor cell samples obtained from 71 dogs with high-grade lymphoma were examined for the expression levels of these genes. Quantitative and conventional reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were used to measure the amounts of p16, p15, and p14 mRNAs. The methylation status of the CpG island of the p16 gene was evaluated using methylation-specific PCR. Overall survival (OS) was compared using the Kaplan-Meier method. The log-rank test and Cox proportional hazard model were used to evaluate factors that influenced OS. Of 62 dogs examined, p16, p15, and p14 mRNA levels were found to be undetectable in 21, 18, and 10 dogs, respectively. In 20/68 dogs analyzed, the CpG island of the p16 gene was shown to be methylated. The prognostic significance of inactivation of the p16, p15, and p14 genes as well as various conventional factors obtained from medical records was examined. p16 expression status and anatomic form/immunophenotype were found to correlate with OS in the dogs with high-grade lymphoma. p16 mRNA level over its cut-off value correlated with a poor prognosis; however, the expression levels of p15 and p14 mRNAs and p16 methylation status did not influence the prognosis in dogs with high-grade lymphoma.