PURPOSE Hepatocellular carcinomas (HCC) are one of the most common cancers in Korea. The mechanism of HCC development is still unclear, and the aberration of the tumor suppressor genes in HCC remains to be clarified. MATERIALS AND METHODS: To study the expressions of p53 and Rb protein, and their correlation with the clinicopathological parameters in HCC, 68 patients, with surgically resected hepatocellular carcinomas, were analyzed by an immunohistochemical method.
The expressions of p53 and Rb protein were classified into three categorizes, depending on the percentage of stained cells. RESULTS: The expression of the p53 protein was 51.5% (35/68), and was significantly correlated with differentiation (p<0.05). The altered Rb protein expression was 72.2% (49/68). The expressions of p53 and altered Rb protein had no significant correlation with the tumor size, gender, WHO histological pattern, cirrhosis or vascular invasion (p>0.05). There was a positive correlation between p53 and Rb protein overexpression (p<0.05). The expressions of p53 and Rb protein had correlation with the Ki-67 labeling index (p<0.05). CONCLUSION: These findings suggest the aberrant expressions of p53 and Rb protein may play a role in the progression and carcinogenesis of HCC.
Citations
Citations to this article as recorded by
Clinical significance of down-regulated HINT2 in hepatocellular carcinoma Dong-Kai Zhou, Xiao-Hui Qian, Jun Cheng, Ling-Hui Chen, Wei-Lin Wang Medicine.2019; 98(48): e17815. CrossRef
The retinoblastoma protein (pRb)/cyclin D1/ p16 pathway plays a critical role in controlling the progression from G1 to S phase of the cell cycle. Abnormal expression of the individual components of the pathway has been reported in many human cancers, including the breast. Our aim was to investigate the role of this pathway in tumorigenesis and tumor progression, and to evaluate the value of these oncoproteins as potential prognostic factors in breast cancer. MATERIALS AND METHODS We examined the significance of the p16, pRb, and cyclin D1 expression in 128 cases of invasive breast carcinomas using immunohistochemistry on formalin fixed, paraffin sections. The results correlated with the survival rate and clinicopathologic variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER) and progesterone receptor (PR) content. The negative finding for nuclear staining for pRb and p16 were defined as abnormal. RESULTS Abnormal expression of the p16 and pRb were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between the p16 and pRb expressions. There was no association between the p16 staining and any other parameters, including survival rate, cyclin D1, or clinicopathologic variables. Surprisingly, there was a trend for pRb positive tumors to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grades, and with higher ER and PR expressions. CONCLUSION These findings suggest the p16 may be negatively regulated by the pRb, and that cyclin D1 is involved in the tumor progression in well-differentiated tumors and could be an ER and PR related protein. In a Cox multivariate analysis, the p16, pRb, and cyclin D1 were not independent predictors of patient outcome.
Lung cancer develops through a multistage process involving the accumulation of diverse genetic alterations.
To gain an understanding of the roles played by tumor suppressor gene proteins and proliferating cell nuclear antigen (PCNA) in chemical carcinogen-induced mouse lung tumorigenesis, we examined the expression of retinoblastoma protein (Rb), p53, and PCNA in normal lung tissues and urethane-induced mouse lung tumors. MATERIALS AND METHODS ICR mice were given urethane by intra-peritoneal injection, and sacrificed at 5, 13, 21, 31, and 37 weeks following treatment. Sequential morphological changes and the immunohistochemical expression of Rb protein, p53, and (PCNA), during mouse lung tumorigenesis, were examined. RESULTS During the carcinogenesis, sequential histological changes from hyperplasia of type II pneumocytes, to adenomas, and ultimately to overt adenocarcinomas were noted. Intense nuclear staining of the Rb protein was observed in normal and hyperplastic alveolar epithelial cells and adenomas. In adenocarcinomas, the Rb protein expression was significantly diminished. The p53 mutant protein was not detected in any lesion. The PCNA labeling index increased along with the advance in the histological grade. CONCLUSION The above results indicate that mouse pulmonary adenocarcinomas develop through premalignant lesions, and down-regulation of the Rb protein expression may be implicated in the urethane-induced mouse lung tumorigenesis.
In addition, the PCNA labeling index may reflect the malignant potential during the tumor progression.
Citations
Citations to this article as recorded by
Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis Jong Wook Shin, Soo Hwan Lee, Eon Sub Park Tuberculosis and Respiratory Diseases.2007; 63(3): 251. CrossRef
PURPOSE To investigate the prognostic role of apoptosis and to evaluate the relationship between apoptosis and apoptosis-related genes, as well as cell proliferation in renal cell carcinoma (RCC). MATERIALS AND METHODS Apoptosis was detected by using the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) technique in 67 formalin-fixed and paraffin-embedded RCC specimens. Immunohistochemical stainings for p53 and retinoblastoma (Rb) proteins and proliferating cell nuclear antigen (PCNA) were also conducted simultaneously. RESULTS The apoptotic index (AI) varied from 0.2% to 25.5%.
The PCNA index (PI) ranged from 2.1% to 70.3%. The expression of p53 protein was found in 31 of 67 (46.3%) cases. Abnormal expression of Rb was seen in 23 of 67 (34.3%) cases. There was a statistically significant positive correlation between AI and increasingnuclear grade (p<0.001). A significant correlation was found between AI and PI (r=0.329, p<0.01). When comparing the AI with the expression of p53 and Rb proteins, there was no significant difference. In univariate survival analysis, nuclear grade, TNM stage, PI, expression of Rb and AI were significantly associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis. CONCLUSION The present findings indicate that apoptosis in RCC is closely associated with cell proliferation, but not with the expression of p53 and Rb proteins. In multivariate analysis, the AI does not carry an independent prognostic significance.