Abstract
BackgroundNasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown. This study was aimed to investigate the association between p63 and NPC.Resultsp63 was expressed in 100%(202/202) of nasopharyngeal carcinoma (NPC) tissues but not in 29 nasopharynx inflammation and 17 non-cancerous nasopharyngeal epidermises on a tissue microarray by immunohistostaining. Further investigation suggested that the p63 expression was associated with the differential stage of NPC: p63 strong staining in Keratinizing squamous cell carcinoma, differentiated non-keratinizing NPC and undifferentiated non-keratinizing NPC presented the percentage of 5/8 (62.5%), 43/48 (92.5%) and 50/50 (100%), respectively. A significant difference (p = 0.001) existed between the keratinizing and non-keratinizing groups. No pathogenic mutations were detected in p63 gene in 12 primary NPC tissues and matched peripheral blood lymphocytes (PBL). Half-life measurement study revealed distinct stability of p63 protein in the different cell lines, especially between the carcinoma cell lines with EBV infection and the non-cancerous cell lines. The results of immunoprecipitation suggested a direct interaction between Epstein-Barr virus nuclear antigen 5 (EBNA-5) and p63 protein in NPC, and this binding would increase the stability of p63.ConclusionOur data suggested p63 might be used as an adjunct diagnostic marker of NPC and contributed a new way to understand the contribution of the EBV in the pathogenesis of NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown
Nasopharyngeal carcinoma (NPC) is an epithelial cancer, the histology of which ranges from well-differentiated, keratinizing squamous cell carcinoma to undifferentiated, non-keratinizing carcinoma according to the World Health Organization (WHO) histological classification of
The tumor suppressor gene p53 is mutated in more than 50% of human cancers [8] and 69% of human head and neck squamous cell carcinomas(HNSCC) [9]; but it was rarely mutate in NPC [10,11,12,13]. p63 was identified on the basis of the structural similarity to the p53 tumor suppressor protein
Summary
Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown. Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. Nasopharyngeal carcinoma (NPC) is an epithelial cancer, the histology of which ranges from well-differentiated, keratinizing squamous cell carcinoma to undifferentiated, non-keratinizing carcinoma according to the World Health Organization (WHO) histological classification of (page number not for citation purposes). The tumor suppressor gene p53 is mutated in more than 50% of human cancers [8] and 69% of human head and neck squamous cell carcinomas(HNSCC) [9]; but it was rarely mutate in NPC [10,11,12,13]. P63 was identified on the basis of the structural similarity to the p53 tumor suppressor protein. Over-expression of p63 was observed in many human cancers, especially these less differentiated tumors [19,20,21,22,23,24]
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