Assessment of p53 expression in nasopharyngeal carcinoma*1

Sheu, Lai-Fa; Chen, Ann; Tseng, Hui‐Hwa; Leu, Fur-Jiang; Lin, John K.; Ho, Kou-Chieh; Meng, Ching-Liang

doi:10.1016/0046-8177(95)90137-x

Cited by 72 publications

(64 citation statements)

References 22 publications

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“…Immunohistochemistry for p53 expression showed that many of the malignant epithelial cells in the tumours expressed readily detectable levels of nuclear p53 (summarized in Table 2). Again this was consistent with previous reports (Niedobitek et al, 1993;Sheu et al, 1995;Murono et al, 1999).…”

supporting

confidence: 94%

“…Characteristically these undi erentiated tumours include a signi®cant in®ltration of T lymphocytes (reviewed in Niedobitek et al, 1996), up to 60% fail to express the tumour suppressor protein p16 INK4A (Lo et al, 1995(Lo et al, , 1996Sun et al, 1995;Gulley et al, 1998) and ± unlike most human tumours ± nearly 100% are wild type for the p53 tumour suppressor gene (E ert et al, 1992;Sun et al, 1992;Lo et al, 1992;Spruck et al, 1992). Paradoxically and in contrast to most normal tissues, although only wild type p53 alleles are present, in most NPC su cient p53 is expressed for it to be detectable by immunohistochemistry (Niedobitek et al, 1993;Sheu et al, 1995;Murono et al, 1999). Since these cells are rapidly proliferating, the p53 protein is assumed to be inactivated.…”

mentioning

confidence: 99%

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High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

et al. 2000

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supporting

confidence: 94%

mentioning

confidence: 99%

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

et al. 2000

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“…This percentage was higher than that of a Greek study where 15.9% of reactivity was observed 33 but lower than other study conducted in Taiwan where the positivity of p53 was estimated at 95% 38 . This difference in p53 expression levels cannot be entirely explained by the antibody clone used since, although we used the DO-1 clone while the majority of the studies carried out used the anti-p53 DO-7 clone, a comparative research have shown that these two antibody clones had the same detection sensitivity and specificity 39 .…”

Section: Discussioncontrasting

confidence: 74%

Immunohistochemical expression of latent membrane protein 1 (LMP1) and p53 in nasopharyngeal carcinoma: Moroccan experience

Tabyaoui¹,

Serhier²,

Sahraoui³

et al. 2013

Afr H. Sci.

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Background: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor intimately associated with Epstein-Barr virus (EBV). NPC is a characteristic tumor displaying epidemiological, genetic and regional distribution properties that makes it unique by its natural behavior. Objectives: To assess the expression pattern of LMP1 and p53 proteins in the different histological types of NPC in a sample of the Moroccan population and to define any association between the expression of those proteins with the sex, the age and the histological types of NPC. Methods: Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 23 Moroccan patients for the presence of LMP1 and p53 using immunohistochemistry (IHC). Results: No LMP1 expression was observed whereas 8 of 23 cases (34. 7%) had detectable p53 protein in the nuclei of tumor cells. After statistical analysis according to the Fisher's exact probability test, no significant association between p53 expression and histological type, age and sex distributions was demonstrated (p>0.05). Conclusion: This study confirms that p53 overexpression is present in a subset of Moroccan NPC patients. Our results are consistent with those reported by other studies concerning the same NPC endemic risk area and provide original data concerning Morocco.

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“…Overexpression of p53 protein has been found in NPC, but its prognostic significance is controversial. Theoretically, overexpression of p53 protein might increase radioresistance; however, its implication on patients with NPC may change from one to another (16,(35)(36)(37)(38). The reason may be related to the population involved and the defined criteria of p53 overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…Screen for p53 mutations in the hot-spots for mutation revealed only a low frequency of p53 mutations ranging from 0 to 10%, which might explain the initial high sensitivity observed with cisplatin-based induction chemotherapy that achieves a 75-100% objective response rate even in locally advanced disease (11)(12)(13)(14). As compared to other types of cancer, numerous studies showed an overexpression or accumulation of p53 protein in >95% NPC (15,16). From the clinical viewpoint, some reports have shown that p53 expression has no prognostic significance for NPC patients (17,18).…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of p53 in nasopharyngeal carcinoma by stable shRNA expression

Sun

Yi²,

Yang³

et al. 2009

Int J Oncol

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Abstract. Nasopharyngeal carcinoma (NPC) is a highincidence malignancy in Southern China and Southeast Asia. Although mutation of p53 tumor-suppressor gene is a rare event in NPC, NPC has a high frequency of over-expressed/ accumulated p53 protein, which was reported to be dysfunction or inactivation in most of NPC. We report here a functional characterization of p53 in an undifferentiated NPC cell line CNE2. To elucidate the biological function of p53, we employed the RNA interference (RNAi) approach to knockdown the endogenously expressed p53 in CNE2 cells. Interestingly, suppression of p53 expression in CNE2 cells was associated with significant down-regulation of p21 WAF1/CIP1 expression and decreased HDM2 protein level in both steady state and genotoxic stress induced by ionizing radiation (IR). Consistent with these biochemical data were the accelerated cell cycle progression and the increased proliferation rate, suggesting that p53 retained growth inhibitory activity in CNE2 cells. Indeed, down-regulation of p53 in CNE2 enhanced the ability of CNE2 cells to grow anchorage-independently in vitro and to develop tumors in vivo. Together with the radioresistance acquired by CNE2sip53 cells, our data indicate that in contrast to a previous study, p53 in this NPC cell line remains functional, which may have an important therapeutical implication. IntroductionNasopharyngeal carcinoma (NPC) is featured by a remarkable racial and geographic distribution, and is a high-incidence malignancy in Southern China, Southeast Asia, Northern Africa, and Alaska, where the observed incidence rates range from 15 to 50 per 100,000 persons (1-3). NPC can occur in all age groups, but has a bimodal age distribution. The incidence peaks at 50 to 60 years of age; and a small peak is observed during late childhood (3). As an etiologically multi-factorial disease, carcinogenesis of the nasopharynx may result from combined effects of Epstein-Barr viral (EBV), genetic and environmental factors (4-7). Available information on the origin of NPC suggests that genetic alterations of tumor suppressor genes and proto-oncogenes in multiple cellular pathways may be important in multistage NPC carcinogenesis.p53 tumor-suppressor protein plays a pivotal role in regulating cell cycle, differentiation and apoptosis (8). As a transcription factor, p53 can induce the expression of p21 WAF1/CIP1 , which inhibits cyclin-dependent kinases, thereby preventing the phosphorylation of Rb and subsequent cell cycle arrest (9). Mutation of p53 tumor-suppressor gene has been found to be the most frequent genetic alteration in human malignancy. p53 mutations often result in accumulation of the mutant p53 protein, which either loses tumor suppressor function or gains oncogenic activity (10). p53 can also be functionally inactivated by mechanisms other than gene mutation (10). Screen for p53 mutations in the hot-spots for mutation revealed only a low frequency of p53 mutations ranging from 0 to 10%, which might explain the initial high sensitivity observed with ci...

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Assessment of p53 expression in nasopharyngeal carcinoma*1

Cited by 72 publications

References 22 publications

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

Immunohistochemical expression of latent membrane protein 1 (LMP1) and p53 in nasopharyngeal carcinoma: Moroccan experience

Functional characterization of p53 in nasopharyngeal carcinoma by stable shRNA expression

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