refers to an increase in the levels of the p53 protein, which is a crucial tumor suppressor involved in regulating the cell cycle, promoting DNA repair, and inducing apoptosis (programmed cell death) in the presence of genomic damage.
🔬 Basic Biology of p53 Gene: TP53 (on chromosome 17p13.1)
Protein: p53, often dubbed the “guardian of the genome”
Function: Acts as a transcription factor that responds to cellular stress.
🧬 Causes of p53 Overexpression TP53 mutation:
Most common cause.
Mutated p53 protein is often non-functional but accumulates in the cell due to its prolonged half-life.
Seen in many cancers (e.g., glioblastoma, breast, lung, colon).
Non-mutational stress:
DNA damage, oncogene activation, or hypoxia can lead to p53 stabilization and transient overexpression.
Loss of MDM2 function:
MDM2 is a negative regulator that targets p53 for degradation.
Loss or inhibition of MDM2 can result in p53 accumulation.
🔍 Detection Immunohistochemistry (IHC):
Common method for identifying p53 overexpression in tumor tissues.
High staining intensity suggests accumulation, often correlating with mutation.
🧠 Clinical Implications Prognostic marker:
Overexpression often correlates with poor prognosis, especially when due to mutation.
Diagnostic aid:
Helps in differentiating tumor types, especially in neuro-oncology (e.g., distinguishing between low- and high-grade gliomas).
Therapeutic target:
Trials are ongoing for drugs that can restore normal p53 function or exploit mutant p53 pathways.