A research team evaluated methods for detecting tumor protein p53 (TP53) mutations by either immunohistochemistry (IHC) of the protein or sequencing of the TP53 gene for missense mutations, and found both methods to be relatively reliable at detecting TP53 alterations. Effects of TP53 alterations also were demonstrated on survival in patients with mantle cell lymphoma (MCL). The results of this study were recently published in the British Journal of Haematology.
According to the researchers, missense mutations in the TP53 gene are often associated with poorer prognosis in patients with MCL, and outcomes can differ by treatment in patients with these mutations. Targeted sequencing of the TP53 gene is often not provided in clinics. However, protein arising from missense mutations may accumulate as deposits in cells that are detectable through IHC, which can be more readily performed, the researchers explained in their report.
In this study, the researchers evaluated eligible patient samples obtained from 3 sources: the Biobank of Lymphomas in Southern Sweden (BLISS; 140 patients), the Nordic MCL 2/3 clinical trials including patients with MCL (216 patients), and a Finnish MCL population-based cohort (84 patients).
Sequencing and IHC analyses were performed on 65 samples from the BLISS cohort and on 69 samples from the clinical trials. The 84 samples from the Finnish cohort were tested only by IHC. In total, 317 samples where tested through IHC and 255 were sequenced.
The researchers reported an accuracy of 82% in predicting TP53 missense mutations based on p53 expression as determined by IHC. In receiver operating characteristic analysis, the area under the curve (AUC) was 0.96 when tested on samples from the BLISS cohort. When performed on Nordic MCL 2/3 samples, the AUC was 0.88.
In the BLISS cohort, 21% of patients with MCL had TP53 mutations in tumor cells, 73% of which were missense mutations. The rate of p53 overexpression in the BLISS cohort was 14%, and in the overall study it was 13%. In univariate analysis, p53 expression and TP53 mutations were associated with an effect on overall survival, with each giving a hazard ratio of 3.1 (P <.001 for each, in comparison with the absence of an aberration).
“Our present results show that p53 IHC analysis can be used as a surrogate marker for the detection of missense mutations,” the researchers wrote. They indicated IHC performed on p53 may serve to aid in treatment decisions for patients with MCL.
Rodrigues JM, Hassan M, Freiburghaus C, et al. p53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma. Br J Haematol. Published online August 4, 2020. doi:10.1111/bjh.17023