• Biomedical Science Letters
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• v.19 no.4
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• pp.348-352
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• 2013

microRNAs (miRNAs) play pivotal roles in controlling cell proliferation and differentiation. miRNA expression in human is becoming recognized as a new molecular mechanism of carcinogenesis. microRNA-34a (miR-34a), a member of the p53 network, was found to be regulated in multiple types of tumor. The purpose of this study was to define roles of miR-34a expression in cervical intraepithelial neoplasia with human papillomavirus infection, and its relationship with p53 protein expression. This study was performed to analyze expression of miR-34a by using qRT-PCR, and to evaluate p53 protein expression by using immunohistochemistry in 40 cases. Down-regulation of miR-34a expression was detected in 27 (67.5%) out of 40 cases and Immunoreactivity for p53 was found in 17 (42.5%) out of 40 cases. Nineteen (82.6%) of the 23 cases with a negative p53 expression showed a down-regulation miR-34a expression, there was a significant associations between miR-34a and p53 protein expression (P=0.04). These results suggest that miRNA-34a expression tend to be reduced depending on the advanced histologic grade, and down-regulation of miR-34a expression might be associated with inactivation of p53 protein expression by human papillomavirus infection.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7737-7741
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• 2013

Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

• Korean Journal of Bronchoesophagology
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• v.4 no.1
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• pp.73-78
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• 1998

The mutation of p53 is the most common genetic alteration found in human cancers and has oncogenic properties. mdm-2 is a recently discoverd that controls the p53 activity by binding of its protein, so negative feedback loop has been suggested in which p53 induces mdm-2 expression. The purpose of this study was to analyze the expression of p53 in leukoplakias, mdm-2 in squamous cell carcinomas, and relationship between p53 and mdm-2 expression in leukoplakias and squamous cell carcinomas. The results were as follows : 1) The p53 was expressed 33.4% in leukoplakias 2) The mdm-2 was expressed 8.3% in leukoplakias and 22.7% in squamous cell carcinomas. 3) The expression rate of p53 was higher in specimens negative for mdm-2 than in specimens positive for mdm-2, but there was not significant relationship between p53 and mdm-2 expression. In conclusion p53 was thought to participate in early phase of oncogenesis, and mdm-2 was thought to have a role as a oncogene in squamous cell carcinoma of head and neck. Though there was not significant relationship between p53 and mdm-2 expression, mdm-2 was thought to inhibit p53 activity.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.2
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• pp.128-135
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins by immunohistochemical staining and tumor prognostic factors including the tumor size, histological differentiation and Dukes' stage of tumor prognostic factors in colon cancer, and to acquire necessary data for the presumption of diagnosis, treatment and prognosis of colon cancer patients. From January 2000 to January 2003 at Hanyang University Guri Hospital, the paraffin blocks of 35 patients diagnosed with colon cancer whose pathologic reports were possible to review were selected. Harris hematoxylin & eosin (H&E) staining and immunohistochemical staining by ABC (Avidin Biotin Conjugate) method were performed. The histological differentiation grade and stage were classified according to the classification of the World Health Organization (WHO) and modified Dukes's stage from H&E staining. The expression rate of p53 and p21 proteins were analyzed by immunohistochemical staining. The results was analyzed statistically by SPSS (Windows version 8.0). As a result, the expression rate of p53 protein was 11.4% (4 cases) in clear differentiation, 48.6% (17 cases) in moderate differentiation, and 17.1% (6 cases) in poor differentiation. In other words, the poorer the differentiation, the higher the expression rate of p53 protein (p<0.05). The expression rate of p21 was 17.1% (6 cases) in clear differentiation, 40.0%(14 cases) in moderate differentiation, and 8.6% (3 cases) in poor differentiation, According to the progression of histological malignant degeneration, the expression rate of p21 protein decreased distinctively (p<0.05). However, the correlation between the two above mentioned proteins and the tumor-size and Dukes' stage was not of statistical significance. In the comparison of the expression rate of p53 protein with that of p21 protein, in 10 cases, p53 protein expression was positive while p21 protein expression was negative, and in 6 cases, p53 protein expression was negative whereas p21 protein expression was positive. Consequently a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed (p<0.05). In conclusion, we found a significant correlation between histological differentiation and the expression rate of p53 and p21 proteins (p<0.05), and a significant inverse correlation between the expression rate of p53 protein and that of p21 protein (p<0.05). Also, it could be confirmed that the over expression of p53 and p21 proteins is closely associated with the occurrence of colon cancer and its progress. Therefore, it is thought that this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• Korean Journal of Bronchoesophagology
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• v.7 no.2
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• pp.152-160
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• 2001

The presence of HPV DNA and the expression of p53 protein and proliferating cell nuclear antigen(PCNA) in head and neck squamous cell carcinoma were determined to evaluate the relationship of these factors and their association with their pathologic stages and cervical lymph node metastasis. Among 65 patients the presence of HPV DNA was found in 12 cases(18.5%), p53 was found positive in 32 cases(49.2%) and expression of PCNA was observed in 24 cases(36.9%). The expression of PCNA was more frequent in the HPV positive cancers compared with the HPV negative ones(p =0.0018), and p53 revealed its higher rate of cooccurrence with the expression of PCNA(p =0.008), which might suggest that PCNA expression has a positive relationship with HPV and p53 mutation in head and neck cancer. There might be inverse relationship between HPV and p53 mutation(p =0.063), but 3 cases showed both HPV DNA positivity and p53 expression. HPV was detected at a higher rate in the early pathologic stages than in the advanced stages of cancer, and p53 expression was more frequently found in the advanced stages(p =0.044). These results suggests that HPV and p53 mutation might have different etiologic roles in the development of head and neck cancer, or cases with p53 mutation might have more aggressive behavior. PCNA expression showed no difference between early and late stages of cancer, and between cases with and without cervical lymph node metastasis.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.1-6
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• 1998

Purpose : To determine the incidence and prognostic effect of p53 expression in patients with advanced supralottic cancer. Materials : Twenty-one cases of total 48 advanced supraglottic cancer patients who received postoperative adjuvant radiation therapy were evaluated by immunohistochemical staining employing p53 monoclonal antibody. Result : Three out of six stage III patients and four out of fifteen stage IV patients showed p53 expression without statistically significant difference (p=0.608). Five year survival rates are $93\%$ in p53 negative, $80\%$ in p53 positive patients and there was no significant difference(p=0.776). p53 expression does not show statistically significant correlation with primary tumor status(p=0.877), lymph node status(p=0.874) and age(p=0.64). Conclusion : There was no statistically significant correlation between traditionally known risk factors and p53 expression.

• Biomedical Science Letters
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• v.16 no.4
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• pp.307-310
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• 2010

Apoptosis is an important significance in the pathogenesis of cancer. Caspase 3 and p53 have been identified as important members of the apoptosis related proteins. This study was performed to define roles of caspase 3 expression and its relationship with p53 expression in endometrial cancers by immunohistochemistry. Immunoreactivity for caspase 3 was found in 13 (65.0%) out of 20 endometrial hyperplasia cases and 8 (36.4%) out of 22 endometrial cancers. Seven (87.5%) of the 8 cases with a positive caspase 3 immunoreactivity showed a positive p53 expression in 22 endometrial cancers. There were no significant associations between caspase 3 and p53 expressions. These findings suggest that caspase 3 expression might be associated with carcinogenesis of endometrial cancers. Further studies are needed to define the relationship between caspase 3 and p53 and apoptosis for examining the mechanisms of tissue-specific apoptosis related protein.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.659-668
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• 1993

Background: p53 is currently considered as a tumor suppressive gene product, and its alterations are suggested to be involved in several human malignancies, including non-small cell lung cancers. p53 expression rates are variable in many reports and among cell types. Also, whether the phase of p53 expression is early or late during carcinogenesis is not certain. Thus, We have investigated to evaluate p53 expression rates of the various cell types and tissues and identify expression phase (early or late). Method: We obtained 71 tissue from 50 non-small cell lung cancer patients and performed the simple immunohistochemical staining using nonspecific monoclonal antibody(NCL-p53DO7). Results: 1) In non-small cell lung cancer patients. the expression rate of lungs(46.5%) is higher than that(25.0%) of lymph nodes. But, there is no significant difference between two groups. 2) Among the various cell types, p53 expression rates in squamous cell carcinoma and adenocarcinoma are 58.3% and 50.0% respectively without significant difference. 3) p53 expression rates in various stages are 33.3%, 60.0%, 40.0%, 60.0% and 66.7% in stage I, II, IIIa, IIIb and IV, respectively with no significant difference. 4) p53 expression rates in the various T parameters are 33.3%, 50.0%, 16.7% and 100% in T1, T2, T3 and T4, respectively and p53 expression rates in the various N parameters are 27.3%, 22.2% and 25.0% in N1, N2 and N3, respectively. There are no significant differences in the expression rates among varous T & N parameters. 5) p53 expression rates of lymph nodes in patients who have positive stains in lungs are 12.5% and 50.0% in N1 and N2. 6) p53 expression rates of all lymph nodes in patients who have negative stains in lungs are 0.0%. Conclusion: The above results show that p53 expression rate in non-small cell lung cancers is not correlated with cell type and progression of stage and it is thought to need further investigations about at what phase p53 expression influences the development and progression of lung cancers.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.365-369
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• 2010

In this study, we examined whether melatonin promotes apoptotic cell death via p53 in prostate LNCaP cells. Melatonin treatment significantly curtailed the growth of LNCaP cells in a dose- and time-dependent manner. Melatonin treatment (0 to 3 mM) induced the fragmentation of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, caspase-8, and caspase-9. Moreover, melatonin markedly activated Bax expression and decreased Bcl-2 expression in dose increments. To investigate p53 and p21 expression, LNCaP cells were treated with 0 to 3 mM melatonin. Melatonin increased the expressions of p53, p21, and p27. Treatment with mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that the melatonin-induced apoptosis was p21-dependent, but ERK-independent. With the co-treatment of PD98059 and melatonin, the expression of p-p53, p21, and MDM2 did not decrease. These effects were opposite to the expression of p-p53, p21, and MDM2 observed with SP600125 and SB202190 treatments. Together, these results suggest that p53-dependent induction of JNK/p38 MAPK directly participates in apoptosis induced by melatonin.