TP53 Mutation in Correlation to Immunohistochemical Expression of P53 Protein in Patients with Hepatocellular Carcinoma

BACKGROUND: Mutations causing p53 inactivation are among the most common genetic alterations in human malignant tumours including hepatocellular carcinoma. Detection of p53 gene mutations in patients with hepatocellular carcinoma (HCC) should provide relevant data for the patients from the Republic of Macedonia and should allow the survivals additional therapeutic option as is gene therapy. AIM: We aimed to detect p53 gene mutations in HCC tissue, and to correlate them with the immunoexpression of p53 protein and multiple clinicopathologic characteristics of a tumour. MATERIAL AND METHODS: We analysed thirty patients with HCC for multiple clinic-pathological characteristics. Tumour tissue samples were immunostained for p53 and detection of p53 gene mutations was performed by polymerase chain reaction followed by Sanger sequencing. RESULTS: Changes in p53 gene sequence were detected in four patients (13.33%), one of them a polymorphism and the other three were missense point mutations with p53 immunoexpression of 50%, 0%, 0% and 90%, respectively. All patients with p53 mutations had cirrhosis. Two of them had Hepatitis B infection, moderately differentiated tumour and T2 status. There was one case with a well-differentiated tumour and one with T4 status. All of them were with vascular invasion. The size of the tumours was in the range of 2.5 cm to 16 cm. All 3 mutations were located in exon 7. CONCLUSION: Mutations in p53 gene are not always associated with obviously altered immunoexpression of p53 protein. Detection of p53 gene mutations is necessary in each case because the new therapeutic modalities offer to apply gene therapy.