Correlation of p53 immunohistochemistry with TP53 mutational status and overall survival in newly diagnosed acute myeloid leukaemia

Abstract

Aims TP53‐mutated acute myeloid leukaemia (AML) is associated with an adverse prognosis and poor response to traditional chemotherapy regimens. Next‐generation sequencing (NGS) is considered the gold standard method to determine TP53‐mutational status; however, molecular assays are costly and time‐consuming. In contrast, immunohistochemistry (IHC) can be performed within 1 day of biopsy. We sought to determine an optimal threshold of staining with p53 IHC to predict TP53‐mutational status. Methods and results We identified 142 consecutive patients with newly diagnosed AML with concurrent NGS analysis diagnosed between 2019 and 2020. All cases were stained for p53 IHC and images were scored for the percent of strongly stained p53+ cells by a combination of manual counting and image analysis. We then correlated percent positive staining with mutational status and clinical outcomes. We determined that a threshold of ≥7% strongly stained cells by p53 IHC correlated with the presence of a TP53 mutation with a sensitivity of 67%, specificity of 100%, positive predictive value of 100% and negative predictive value of 90%. TP53 mutation and the presence of ≥7% staining by IHC were associated with shorter overall survival by univariate analysis (P < 0.01). Conclusion If the limitations of this study are carefully considered, our findings suggest that p53 protein expression as evaluated by IHC could be used to rapidly predict TP53‐mutational status with high specificity and assist in risk stratification in newly diagnosed AML.

The Value of Tailored Therapy on Survival in High Risk MDS with Del5q: Report of an Unusual Case

“…In conclusion, we report on a high-risk MDS patient harbouring a del (5q) abnormality, which confers a poor prognosis on the outcome of this neoplasm. In addition, our patient presented a negative TP53-mutational status, evaluated by immunohistochemically TP53 expression only [12,13]. The hypomethylating agent, azacitidine, represents the treatment of choice to treat high risk MDS, independent of karyotype, allowing for an overall response rate of 56%, including a 5.6% CR as well as a marrow CR rate of 11.1% [1,3,9].…”

“…Karyotype analysis by G band staining on 20 metaphases showed a 46, XX, del (5) (q13q31), confirmed by fluorescence in situ hybridization. BM immunohistochemistry [12,13] ruled out TP53 overexpression (Figure 1). According to the World Health Organization classification of myeloid neoplasms at that time [14], the diagnosis was MDS with excess blasts-2 (EB-2).…”

Utilizing digital pathology and immunohistochemistry of p53 as an adjunct to molecular testing in myeloid disorders

“…4 C and D where we note poor correlation between digitally analyzed IHC and overall blast counts and molecular findings despite the intuitive assumption that those metrics would correlate with one another. As others have noted, 9 this is likely due to a host of molecular and cellular factors that cannot be assessed by simple staining techniques. As p53 is subject to rapid protein turnover leading to variable levels of expression within “normal cells,” the nature of the individual mutation(s), the presence of additional pathologic or benign genetic variants within an individual, staining abnormalities, etc., seemingly prevent IHC from accurately reflecting mutation burden.…”

“…Given these impediments, multiple groups have investigated the utility of alternative approaches such as immunohistochemistry (IHC) in identifying and monitoring TP53 mutations, with several groups reporting strong correlations between IHC and molecular testing. 6 , 7 , 8 , 9 This approach provides a rapid and cost-effective alternative to molecular testing in areas where it is not immediately available. Despite the advantages offered by IHC, one limitation to its use is a lack of standardization due to intra- and interobserver variability in interpretation.…”

A DNA damage response‐like phenotype defines a third of colon cancers at onset

“…MSI was scored in the epithelial component as suggested by the antibody provider (Agilent) in the presence of nuclear-positive inflammatory and stromal control cells (https://docum ents.cap.org/docum ents/mmr-msi-teach ing-prese ntati on.pdf; last accessed April 12, 2023). TP53 staining intensity was scored as suggested 23,24 (Figure S2C). MX1 staining was scored in the epithelial compartment semiquantitatively (neg, focal/weak, strong) (Figure S2B).…”