Article

Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma.

State Key Laboratory of Oncology in Southern China, Cancer Center of Sun Yat-Sen University, Guangzhou, China.
Journal of Translational Medicine (Impact Factor: 3.99). 12/2009; 7:110. DOI: 10.1186/1479-5876-7-110
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
136 Views
  • Source
    [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.
    Cancer genetics and cytogenetics 12/2010; 203(2):269-77. DOI:10.1016/j.cancergencyto.2010.08.011 · 1.93 Impact Factor
  • 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
    Geoscience and Remote Sensing Symposium, 2004. IGARSS '04. Proceedings. 2004 IEEE International; 10/2004
  • [Show abstract] [Hide abstract]
    ABSTRACT: The tumor suppressor protein, p53 is regarded as a key player in tumor suppression, as it promotes growth arrest, apoptosis and cellular senescence, while also blocking angiogenesis. The plethora of mechanisms underlying the p53 efficient death response involves transcriptional activation or repression of target genes, as well as the recently identified microRNAs, and transcription-independent functions. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis or atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. The effect of targeting cell death signaling proteins has been established in preclinical models of human diseases. In this regard, therapeutic strategies aimed at reactivation of p53 in tumors emerge as a promising approach for the treatment of cancer patients, as well as chemical inhibitors of p53 that may prove effective in suppressing disorders associated with widespread p53 activation. This review highlights recent developments of p53-induced apoptosis in human diseases. In addition, we will discuss controversies arising from the double-edge sword of targeting p53 in disease. Finally, ursodeoxycholic acid (UDCA), an endogenous bile acid used to treat cholestatic liver diseases, was recently described as a fine modulator of the complex control of p53 by Mdm-2. We will also review recent therapeutic strategies and clinical applications of targeted agents, and their progress in drug lead discovery, with particular emphasis on the potential use of UDCA.
    Current pharmaceutical design 07/2010; 16(22):2493-503. DOI:10.2174/138161210791959818 · 3.29 Impact Factor