Journal of Experimental Research on Human growth & Aging (JERHA)

Research Article

Key Molecules Involved in Signalling Transduction Pathways of Nasopharyngeal Carcinoma

Authors: Mihai Ceausu* , Maria Neagu and Maria Bosa

Abstract

The association of nasopharyngeal carcinoma with EBV infection has created along the time a paradigm, due to an extensive use of both serologic tests and IHC or ISH, for detection and screening the high risk population, even if in the last 2 decades, the incidence of this type of cancer has decreased with 30%. A study group of 53 archived formalin-fixed paraffin-embedded samples of undifferentiated nasopharyngeal carcinoma have been assessed using standard HE stain and immunohistochemistry for 4 monoclonal antibodies: EBV latent membrane protein 1-LMP1, multidrug resistance protein-MRP3, the inducible isoform of COX - COX2 and the nuclear transcription factor NF-kB, simultaneously with RNA transcript of EBV (EBER) using an in situ hybridization technique. A number of direct correlations, statistically significant were noticed between: LMP1 and COX-2 (r = 0.53, p = 0.03), LMP and MRP3 (r = 0.5, p = 0.0004), LMP and NF-kB (r = 0.4, p = 0.001). The ISH reaction for EBER transcript was positive in 22.64% of cases. A low direct correlation, statistically significant was recorded between EBER and LMP (r = 0.31, p =0.03), EBER and MRP (r = 0.4, p = 0.05). Our data suggest that the latent membrane protein of EBV activates the nuclear transcription factor NF-kB, independent of COX-2 overexpression, via a signalling transduction pathway, from viral genome to cellular genome, in highly aggressive tumours. In MRP3 negative neoplastic cells, the NF-kB overexpression is associated with an aggressive potential of the tumour (with an unfavourable prognostic) and an independent relationship between the resistance to chemotherapy and tumour differentiation.

Keywords: Nasopharyngeal Carcinoma; EBV Transcript; Signalling Molecules

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