Predictive value of TP53 RNAscope®in situ hybridization and p53 immunohistochemistry for TP53 mutational status in canine diffuse large B-cell lymphoma

TP53 mutations are associated with short survival and poor treatment response in canine diffuse large B-cell lymphoma (cDLBCL). The expression of TP53 by RNAscope (R) in situ hybridization and p53 by immunohistochemistry (IHC) was investigated in 37 formalin-fixed paraffin-embedded cDLBCL, to assess their correlation with TP53 mutational status and to evaluate their prognostic value. TP53 was detected in all samples by RNAscope (R). Ten of 37 (27%) cases expressed p53 by IHC, with highly variable percentage of positive cells. TP53 RNAscope (R) scores and p53 IHC results were not correlated. The expression of TP53 by RNAscope (R) was not influenced by its mutational status. Conversely, p53 IHC and TP53 mutations were significantly associated. p53 IHC predicted TP53 genetic mutations with high accuracy (97.3%). All TP53-mutated samples carrying missense mutations exhibited p53 expression by IHC, while all wild-type cases and a single case with frameshift insertion were negative. In univariable analysis, p53 IHC was associated with shorter time to progression (TTP) and lymphoma-specific survival (LSS). Nevertheless, in multivariable analysis, only treatment significantly affected TTP and LSS. These findings suggest p53 IHC is an accurate, cost-effective tool for predicting TP53 mutations in cDLBCL, unlike TP53 RNAscope (R), though its prognostic value requires further validation.