Zhang MF, Zhang ZY, Fu J, Yang YF, Yun JP.. Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma. J Transl Med 7: 110

State Key Laboratory of Oncology in Southern China, Cancer Center of Sun Yat-Sen University, Guangzhou, China.
Journal of Translational Medicine (Impact Factor: 3.93). 12/2009; 7(1, article 110):110. DOI: 10.1186/1479-5876-7-110
Source: PubMed


Tumor Protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21/WAF1), and murine double minute 2 (MDM2) participate in the regulation of cell growth. Altered expression of these gene products has been found in malignant tumors and has been associated with poor prognosis. Our aim was to investigate the expression of the 3 proteins in hepatocellular carcinoma (HCC) and their prognostic significance.
We examined p53, p21/WAF1, and MDM2 expression in 181 pairs of HCC tissues and the adjacent hepatic tissues by performing immunohistochemistry and examined the expression of the 3 proteins in 7 pairs of HCC tissues and the adjacent hepatic tissues by using western blot analysis.
The expression of p53, p21/WAF1, and MDM2 in the HCC tissues was significantly higher than those in the adjacent hepatic tissues (P < 0.05). A statistical correlation was observed between p53 and p21/WAF1 expression in HCC tissues (R = 0.195, P = 0.008). A statistical correlation was observed between expression of p53 and p21/WAF1 (R = 0.380, P = 0.000), p53 and MDM2 (R = 0.299, P = 0.000), p21/WAF1 and MDM2 (R = 0.285, P = 0.000) in 181 liver tissues adjacent to the tumor. Patients with a low pathologic grade HCC (I+II) had a higher tendency to express p53 on tumor cells than the patients with high pathologic grade HCC (III+IV) (P = 0.007). Survival analysis showed that positive p21/WAF1 expression or/and negative MDM2 expression in HCC was a predictor of better survival of patients after tumor resection (P < 0.05).
The proteins p53, p21/WAF1, and MDM2 were overexpressed in all the HCC cases in this study, and p53 and p21/WAF1 overexpression were positively correlated. The expression of p21/WAF1 and MDM2 can be considered as 2 useful indicators for predicting the prognosis of HCC.

Download full-text


Available from: Chris Zhiyi Zhang
  • Source
    • "It has been reported that MDM2 protein is overexpressed in HCC tissue. In a previous report by MF Zhang's group, MDM2 expression was examined in 181 pairs of HCC tissues and the adjacent hepatic tissues by using immunohistochemistry, through which the group found that MDM2 was overexpressed in all the HCC cases [49]. But in another study, the result of immunohistochemistry showed that MDM2 was expressed in 26% of HCC, and its expression correlated positively with p53 mutations [50]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Although new therapeutic strategies have been continuously developed and applied to clinical treatment for HCC, the prognosis is still very poor. Thus, early detection of HCC may enhance effective and curative management. In this study, autoantibody responses to MDM2 protein in HCC patient's serum were evaluated by enzyme-linked immunosorbent assay (ELISA) and part sera were evaluated by Western blotting and indirect immunofluorescence assay. Immunohistochemistry (IHC) over tissue array slides was also performed to analyze protein expression of MDM2 in HCC and control tissues. The prevalence of autoantibodies against MDM2 was significantly higher than that in liver cirrhosis (LC), chronic hepatitis (CH), and normal human sera (NHS). The average titer of autoantibodies against MDM2 in HCC serum was higher compared to that in LC, CH, and NHS. A high titer of autoantibodies against MDM2 in ELISA could be observed in the serum in 6 to 9 months before the clinical diagnosis of HCC in the serum of several HCC patients with serial bleeding samples. Our preliminary data indicate that MDM2 and anti-MDM2 system may be a potential biomarker for early stage HCC screening and immunodiagnosis.
    Full-text · Article · May 2014 · Research Journal of Immunology
  • Source
    • "Deletion of TP53 was negatively associated with survival and with degree of differentiation. Our findings are in consistence with several reports in other populations showing that positive or negative TP53 expression did not correlate with the survival of the patients with HCC [40] [43] [44]. Table 7 Overall period of survival (survival 2) and the clinicopathologic data "
    [Show abstract] [Hide abstract]
    ABSTRACT: Amplification of the two oncogenes ERBB2 and MYC and deletion of the tumor suppressor gene TP53 are frequently encountered in cancerous tissues. The purpose of this study was to use the fluorescence in situ hybridization (FISH) technique for the assessment of ERBB2 and MYC amplification and TP53 deletion, and to relate these molecular markers to clinical and pathologic factors in Saudi patients with hepatocellular carcinoma. The study was conducted on 40 paraffin-embedded tissue samples originally taken from either hepatitis C virus (HCV)- or HBV-infected patients using the FISH technique. The level of ERBB2, MYC, and TP53 in the malignant group was significantly increased as compared to the control group. Of the 40 patients, 3 (7.5%) had amplification of ERBB2 gene, 4 (10%) different patients had amplification of MYC, and 26 patients (65%) had evidence of deletion of at least one allele on chromosome 17 for the TP53 gene in a high proportion of cells. There was a significant correlation between amplification of MYC oncogene and the number of tumor masses. Moreover, significant correlation was observed between poorly differentiated tumors when compared with moderate or well-differentiated tumors when MYC was analyzed. On the other hand, MYC failed to reveal any significant association between oncogene amplification and other clinicopathologic variables examined. Univariate analysis revealed a strong association between deletion of TP53 and multiple tumor mass (P< 0.001). No statistical correlation could be detected between deletion of TP53 and tumor size, grade, stage, and tumor differentiation. No significant difference could be detected in the mean survival time of patients positive for the alteration of the genes compared to the patients who showed no alterations for the same genes. However, when the stage of the tumor was analyzed, there was a significant difference in the mean survival time between patients who showed gene alterations compared to patients with no changes in the studied genes. When overall survival was analyzed, only patients with MYC amplification had a lower median survival (20.75 months) than patients without MYC amplification (35.82, P = 0.009). Genetic alterations of ERBB2 and TP53 genes had no effect on survival 2 (see Results). The combination of ERBB2, MYC, and TP53 could be useful markers to stratify patients into different risk groups.
    Full-text · Article · Dec 2010 · Cancer genetics and cytogenetics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Radar backscattering response has the potential of retrieving desired snow parameters, such as snow water equivalence, snow depth, liquid water content which are important factors in hydrological investigation. The objective of this study is to develop an algorithm which can decompose the scattering of wet snow and also develop new description of surface scattering. There are two scattering sources - the volume scattering component from snow pack and the air-snow surface scattering component - for radar backscattering while observing wet snow. Depending upon which scattering component is dominant and then controls the response to snow wetness, an algorithm can be developed to quantitatively describe the relationship between this two scattering sources and snow wetness. We have established a model - simulated at C-band <sub>a</sub>ta-base by using two scattering components. The database covers the most possible wet snow physical properties and surface roughness conditions. Using this data-base, an inversion algorithm can be developed for using C-band multi-polarization measurements. The newly developed algorithm mainly involved two steps: 1) decomposes the surface and volume scattering signals, and 2) then use each scattering component to estimate snow wetness
    Full-text · Conference Paper · Oct 2004
Show more