• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.189-195
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• 2016

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.4
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• pp.199-205
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• 2003

The p53 protein was discovered in 1979 as cellular 53-kD nuclear phosphoprotein bound to the large transforming antigen of SV40 virus. $P21^{WAF1/CIP1}$, which has been described as the critical downstream mediator of p53, is known to suppress DNA replication and arrest the G1 cell cycle by quaternary complex with cyclin D, cyclin-dependent kinase(CDK) and proliferating cell nuclear antigen(PCNA). In these days, some studies shows that the p21 can be induced by independent pathways. There are various reports about the expression of p21 (67%.82.4%) in oral squamous cell carcinoma. But these studies are mostly done in malignant tumor not in benign tumor. So we decided to study the expression of p21 in ameloblastoma and the relationship between p53 and p21 as a downstream mediator of p53 in ameloblastoma. We investigated the expression of p21 and p53 with the method of immunohistochemistry. We selected 30 cases of ameloblastoma tissue blocks (acanthomatous type: 5 cases, follicular type: 8 cases, plexiform type: 17 cases) imbedded in paraffin. We used 30 cases of normal gingival tissues and 30 cases of squamous cell carcinoma tissues (SCC) respectively and compared their results with those of ameloblastoma. We made slides with the streptavidin-biotin methods and used monoclonal antibody DO-7 (Novocastra, Newcastle, United Kingdom) as p53 antibody and monoclonal antibody M7202 (DAKO, California, U.S.A.) as p21 antibody. We used Pearson's correlation coefficient to analyse the relationship. The results were as follows: 1. p21 was expressed in ameloblastoma about 30% and this is lower than that of normal gingiva and SCC. 2. In normal gingiva and ameloblastoma, p21 expression was correlated with p53 expression. 3. In SCC, p21 were expressed about 83.3% and this is more than that of p53. But there was no correlation between p21 and p53 expression. We confirmed p21 expression and relation with p53 in ameloblastoma. But, to confirm the function of p21, more studies about p21 expression in malignant ameloblastoma and ameloblastic carcinoma are needed.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.56.1-56.6
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• 2019

Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2341-2344
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• 2014

Background: p53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and its significance as a diagnostic marker. Materials and Methods: We compared and evaluated 93 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significance and 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC), 5 follicular adenomas (FA), 5 Hashimoto's thyroiditis (HT) and 12 nodular hyperplasias (NH) for significance as a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffinembedded tissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versus other benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively. Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlation between p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis, extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC from other BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.

• Biomedical Science Letters
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• v.13 no.3
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• pp.213-221
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins, c-erbB-2 oncoprotein and $TGF-{\beta}1$ and tumor prognostic factors in colon cancer including the tumor size, histological differentiation and Dukes' stage. The expression rate of p53 protein was 11.4% (4 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation. In other words, the poorer differentiation, the higher the expression rate of p53 protein (P<0.05). The expression rate of p21 protein was 17.1% (6 cases) at well differentiation, 40.0% (14 cases) at moderately differentiation, and 8.6% (3 cases) at poorly differentiation, indicating that, as the histological malignant degeneration progressed, the expression rate of p21 protein decreased distinctively (P<0.05). However, the correlation of the above mentioned proteins with tumor size and Dukes' stage was not recognized. The expression rate of c-cerbB-2 oncoprotein was 11.4% (4 cases) at well differentiation, 54.3% (19 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation, indicating that the poorer differentiation, the higher expression rate of c-erbB-2 oncoprotein (P<0.05). The expression rate of $TGF-{\beta}1$ was 17.1% (6 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 11.4% (4 cases) at poorly differentiation. As Dukes' stage progressed, the expression rate of $TGF-{\beta}1$ was 8.6% (3 cases) in stage A, 20.0% (7 cases) in stage B, 37.1 % (13 cases) in stage C, and 11.4% (4 cases) in stage D. There was a difference in expression rates between Dukes' stages (P<0.05). In 10 cases, p53 protein was positive while p21 protein was negative, and in 6 cases, p53 protein was negative whereas p21 was positive (P<0.05). Therefore, a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed. In conclusion, since there was a signigicant correlation between histological differentiation of colon cancer and the expressions of p53 and p21 proteins and c-erbB-2 oncoprotein, and between Dukes' stage and the expression of $TGF-{\beta}1$, it was conformed that the overexpression of p53 and p21 proteins, c-erbB-2 oncoprotein, and $TGF-{\beta}1$ is closely associated with the occurrence of colon cancer and its progress. Accordingly, this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.487-498
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• 2016

Leptin, an adipokine predominantly produced from adipose tissue, is well known to induce tumor growth. However, underlying molecular mechanisms are not established yet. While p53 has long been well recognized as a potent tumor suppressor gene, accumulating evidence has also indicated its potential role in growth and survival of cancer cells depending on experimental environments. In the present study, we examined if p53 signaling is implicated in leptin-induced growth of cancer cells. Herein, we demonstrated that leptin treatment significantly increased p53 protein expression in both hepatic (HepG2) and breast (MCF-7) cancer cells without significant effect on mRNA expression. Enhanced p53 expression by leptin was mediated via modulation of ubiquitination, in particular ubiquitin specific protease 2 (USP2)-dependent manner. Furthermore, gene silencing of p53 by small interfering RNA (siRNA) suppressed leptin-induced growth of hepatic and breast cancer cells, indicating the role of p53 signaling in tumor growth by leptin. In addition, we also showed that knockdown of p53 restored suppression of caspase-3 activity by leptin through modulating Bax expression and prevented leptin-induced cell cycle progression, implying the involvement of p53 signaling in the regulation of both apoptosis and cell cycle progression in cancer cells treated with leptin. Taken together, the results in the present study demonstrated the potential role of p53 signaling in leptin-induced tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6039-6045
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• 2012

This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.

• Journal of Chest Surgery
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• v.36 no.12
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• pp.952-960
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• 2003

It has been reported that p53 regulates the G2-M checkpoint transition through cyclin Bl, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The aim of this study is to clarify the role of the cell cycle regulators, cyclin B1 and p53 in patients with esophageal squamous cell carcinoma (ESCC). Material and Method: Tissue samples from 46 patients with ESCC were included in this study. Expression levels of cyclin Bl and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemical study Result: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 10% of tumor cells were cyclin B1 positive in 19 patients (41.3%). Several clinicopathologic parameters, including tumor stage (p<0.05), pathologic Iymph node status (p<0.05) and invasion of Iymphatic vessels (p<0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also correlated with a poor prognosis in patient with ESCC in univariate analysis (p<0.05) and multivariate analysis (p<0.05), In contrast, p53 expression exhibited significant correlation with the level of cyclin B1 expression, but was not associated with prognostic parameters in patients with ESCC. Conclusion: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.88-95
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• 2009

Purpose: p53 and bcl-2 are important markers of apoptosis. The expression of p53 and bcl-2 in gastric adenocarcinoma was examined in relation to prognosis and survival rate. Materials and Methods: The clinicopathologic data from 238 patients who underwent gastrectomies for gastric adenocarcinoma between December 1999 and July 2007 were reviewed. Immunohistochemical staining of gastric adenocarcinoma tissues embedded in paraffin blocks was performed using an Envision kit (DAKO, Glostrup, Denmark). Statistical comparisons were made between age, gender, tumor invasion, lymph node metastasis, TNM stage, Lauren's classification, cell differentiation, and the relationship with p53 and bcl-2. Results: The expression of p53 was related to cell differentiation (P=0.028) and UICC TNM stage (P<0.001). The expression of bcl-2 was related to UICC TNM stage (P=0.005). The co-expression of p53 and bcl-2 was related to UICC TNM stage (P=0.002). The co-expression group exhibited a greater reduction in the survival rate (P=0.001). Conclusion: The expression of p53 and bcl-2 nuclear proteins has significant relationships with other conventional prognostic factors and the survival rate. bcl-2 will be characterized through analysis of a greater number of patients and comparison with survival data over a longer period of time.

• Journal of Life Science
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• v.30 no.12
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• pp.1070-1077
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• 2020

Treatment with anticancer drugs changes the expression of multiple genes related to cell proliferation, migration, and drug resistance. These changes in gene expression may be connected to regulatory networks for each other. This study showed that doxorubicin treatment induces the expression of oncogenic FosB and decreases the expression of oncogenic SETDB1 in A549 and H1299 human lung cancer cells, which are different in tumor suppressor p53 status. However, a small difference was detected in the quantitative expression of those proteins in the two kinds of cells. To examine the potential regulation of SETDB1 and FosB by p53, we predicted putative p53 binding sites on the genomic DNA of SETDB1 and FosB using a TF motif binding search program. These putative p53 binding sites were identified as 18 sites in the promoter regions of SETDB1 and 21 sites in the genomic DNA of FosB. A luciferase assay confirmed that p53 negatively regulated the promoter activities of SETDB1 and FosB. Furthermore, the results of RT-PCR, western blot, qPCR, and immunostaining experiments indicated that the transfection of exogenous p53 decreases the expression of SETDB1 and FosB in H1299 cells. This indicates that p53 negatively regulates the expression of SETDB1 and FosB at the transcriptional level. Collectively, the downregulation of SETDB1 and FosB by p53 may provide functional networks for apoptosis and for the survival of cancer cells during anticancer drug treatment.