High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma

Abstract

To determine the relationship between p53 altered expression and p53 mutations in hepatocellular carcinoma (HCC), we analysed p53 protein immunohistochemically and assessed the presence of mutations in exons 4-8 of the p53 gene using SSCP assay in 117 HCCs corresponding to 78 patients. We also determined the relationship of p53 expression with cellular proliferation by immunostaining with monoclonal antibodies to Ki-67. We found significant levels of p53 protein expression in 23.1% of the 117 cases studied, but identified mutations in only 12 cases (10.3%). Only four of the p53-positive cases had mutations in the regions analysed. Six of the cases that displayed mutations at p53 gene were negative for immunohistochemical analysis (IHC) and two cases showed positive immunoreactivity in the cytoplasm of the cell. In conclusion, strong IHC reactivity for p53 protein is not an indicator of the presence of p53 gene mutations at exons 4-8 in HCC. Thus, p53 loss of function in HCC should be evaluated both by p53 mutation analysis and p53 protein expression, as both give complementary information about p53 status.

Oncogene and therapeutic target analyses in atypical fibroxanthomas and pleomorphic dermal sarcomas

“…However, some TP53 mutated cases were immunohistochemically negative. This discrepancy has been reported by other investigators especially in the case of nonsense, splice and null mutations [9, 10]. The majority of the detected TP53 substitutions demonstrated characteristic UV-induced TP53 mutations taking place at dipyrimidine sites being C to T transitions.…”

Identification of Drivers from Cancer Genome Diversity in Hepatocellular Carcinoma

“…So far, several genes, such as TP53 , CTNNB1 and AXIN1 , are frequently mutated and have been demonstrated to contribute to tumor development. Although TP53 is the most frequently altered gene in HCC [73,74,75,76], its mutation rate is different between geographical regions. While a high frequency of mutations has been reported in patients from East Asia and Africa, it is relatively lower in other countries, including the West [77].…”

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

“…Immunohistochemical staining for antibodies to p53 and Ki-67 (anti-p53 Clon DO-7 and anti-Ki-67 MIB1; DakoCytomation, Carpinteria, CA, USA) were performed using the avidin-biotinperoxidase complex method. 23 The primary antibody was applied to the sections and allowed to react for 25 min at room temperature. The sections were then incubated with biotinylated anti-mouse antibody (1:50 dilution for p53 and 1:200 dilution for Ki-67) for 25 min and avidin-biotin-peroxidase reagent for 25 min.…”

“…Nuclear staining was expressed as a percentage per 100 cells. Cases with greater than 10% nuclear staining of the tumor cells were considered positive 23 …”