p53 immunoreactivity and single-strand conformational polymorphism analysis often fail to predict p53 mutational...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• The p53 tumor suppressor gene is frequently mutated in various cancers, including gastric cancer.
• Accurate detection of p53 mutational status is crucial for understanding gastric cancer progression and developing targeted therapies.

Purpose of the Study:

• To evaluate the efficacy of p53 protein expression (immunohistochemistry) and single-strand conformational polymorphism (SSCP) analysis in predicting p53 gene mutations in archival gastric cancer tissues.
• To compare the diagnostic accuracy of IHC and SSCP with direct sequencing for p53 mutations.

Main Methods:

• Archival paraffin-embedded tissues from 78 advanced gastric cancer patients were analyzed.
• p53 gene mutational status (exons 5-9) was assessed using SSCP analysis and direct sequencing.
• p53 protein expression was evaluated by immunohistochemical analysis (IHC) and scored based on intensity and cell staining.

Main Results:

• p53 gene mutations were detected in 36% of cases by direct sequencing and 23.1% by SSCP, with SSCP missing 38% of mutations.
• Immunohistochemistry (IHC) showed p53 immunoreactivity in 75.6% of cases.
• Concordance between IHC and direct sequencing was 50%, and between IHC and SSCP was 37%. Forty-five percent of IHC-positive cases lacked mutations in exons 5-9, and 5% of IHC-negative cases had mutations.

Conclusions:

• p53 immunoreactivity correlates with p53 gene mutations in only 50% of advanced gastric cancers (exons 5-9), making IHC an unreliable marker.
• The sensitivity of SSCP for detecting p53 mutations is low (62%), rendering it unsuitable for reliable screening.
• Direct sequencing is the preferred method for accurate p53 mutational analysis in gastric cancer research.