Revisiting TP53 Mutations and Immunohistochemistry--A Comparative Study in 157 Diffuse Gliomas

Area of Science:

• Oncology
• Molecular Pathology
• Genetics

Background:

• The correlation between p53 protein expression (immunohistochemistry) and TP53 gene mutations is debated.
• Accurate prediction of TP53 mutation status is crucial for glioma classification and treatment.

Purpose of the Study:

• To re-evaluate the effectiveness of p53 immunohistochemistry (IHC) in predicting TP53 mutation status.
• To establish reliable criteria for using p53 IHC as a surrogate marker for TP53 mutations in diffuse gliomas.

Main Methods:

• Analyzed 157 diffuse gliomas (WHO grades II-IV) using exon-by-exon DNA sequencing of TP53 (exons 4-10) on frozen samples.
• Performed p53 IHC (DO-7 antibody) on paired formalin-fixed paraffin-embedded tissues, assessing staining extent and intensity.
• Utilized Receiver Operating Characteristic (ROC) curve analysis to determine optimal prediction thresholds.

Main Results:

• Detected 72 TP53 mutations in 66 out of 157 diffuse gliomas.
• Strong p53 immunoreactivity in >10% of tumor cells accurately predicted TP53 mutation (sensitivity 78.8%, specificity 96.7%).
• Frameshift mutations were often associated with negative p53 immunostaining.

Conclusions:

• p53 immunohistochemistry serves as a highly specific and moderately sensitive marker for predicting TP53 mutations in diffuse gliomas.
• The proposed cutoff (strong staining in >10% of cells) offers a reliable method for TP53 mutation status assessment.