Western blot analysis of six samples showed a high level of expression of c-myc and cdc2 kinase and a low level of p53 protein in NPCAs that contained both HPV and EBV (n = 3).
Using a previously established simple and sensitive p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases.
Special caution should be taken with patients with cancers such as nasopharyngeal carcinoma in which p53 mutation is infrequent and radiotherapy is the main choice of treatment.
To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z).
In-situ hybridization using oligonucleotide probe to EBV-encoded small RNAs (EBERs) and immunohistochemistry using monoclonal antibodies against EBV latent membrane protein 1 (LMP1), p53 protein and bcl-2 proteins were performed in 56 primary NPCs.
A20 may be a key downstream effector of LMP1 in NPC, as LMP1-induced A20 blocks p53-mediated apoptosis in H1299 epithelial cells and most NPCs have wild-type p53.
Although the involvement of p53 and of the retinoblastoma gene (RB/p105) in NPC has been well studied, there is paucity of mutational data regarding the retinoblastoma-related gene RB2/p130 in primary tumors and particularly in NPC.
Genomic analysis for p53 mutation and in situ hybridization for human papillomavirus showed negative results, indicating that both important molecular events in NPC or head and neck cancer play a small role in this particular type of newly developed second malignant tumor.
We suggest that deltaN-p63 is a good candidate as a suppressor of wild type p53 function in these tumours and also that it may prove to be a valuable diagnostic marker for undifferentiated NPC.
To determine whether p53 was also accumulated in North African NPCs, we investigated its expression, by immunohistochemistry, in a series of 90 Tunisian biopsies.
The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV.
This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy.
To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome.
Collectively, we suggest that the p53 gene polymorphism may associate with NPC susceptibility in Thai population, particularly the Pro/Pro genotype carriers with age of >40 years.
These results indicate that the p53 mutations are an infrequent event in NPC in Spanish patients needing exogenous factors as the EBV infection for the development of this malignancy.
It is theorized that the cooperative expression of bcl-2 and LMP1 exists in the majority of NPC, while a minority of NPC have cooperative expression of LMP1 and mutant p53.
Antisense oligodeoxynucleotides may become a promising strategy to enhance radiosensitivity in nasopharyngeal carcinoma cells with normal p53 function.