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

Vet Q. 2024 Dec;44(1):1-9. doi: 10.1080/01652176.2024.2403453. Epub 2024 Sep 16.

Abstract

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® 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®. Ten of 37 (27%) cases expressed p53 by IHC, with highly variable percentage of positive cells. TP53 RNAscope® scores and p53 IHC results were not correlated. The expression of TP53 by RNAscope® 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®, though its prognostic value requires further validation.

Keywords: Canine diffuse large B-cell lymphoma; TP53; immunohistochemistry; in situ hybridization; mutation; p53.

MeSH terms

  • Animals
  • Dog Diseases* / genetics
  • Dogs
  • Female
  • Immunohistochemistry* / veterinary
  • In Situ Hybridization* / veterinary
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / mortality
  • Lymphoma, Large B-Cell, Diffuse* / veterinary
  • Male
  • Mutation
  • Predictive Value of Tests*
  • Prognosis
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53

Grants and funding

This work was supported by the Italian Ministry of Health under Grant RC IZS VE 04/2020.