Spontaneous apoptosis and expression of apoptosis related proteins in relation to EBV status in primary nasopharyngeal cancer

ABSTRACT

Nasopharyngeal carcinoma [NPC] is an enigmatic tumour due to its unique incidence pattern and the ubiquitious association with EBV, regardless of the geographical origin, radiotherapy is the mainstay of treatment and the major cause of treatment failure is loco-regional recurrence. Hence, we chose to examine the extent of spontaneous apoptosis, the expression of major apoptosis related proteins and their relation to EBV infection in NPC. Expression of Bcl-2 and BAX proteins in 103 NPC was assessed by immunohistochemistry and Apoptotic index [A1] assessed by morphological evaluation. Presence of EBV was assessed by PCR using primers directed against non- polymorphic EBNA-1 gene. Malignant transformation of nasopharyngeal epithelium was associated with a higher expression of the anti-apoptotic protein Bcl-2[p 0.0001] and reduced expression of pro-apoptotic protein BAX [p 0.0001] and reduction in apoptotic index[p0.0001] when compared to bengin lesions. It was interesting to note significant increase of Bcl-2 [p 0.0005] and significant decrease of BAX [p.0.014] and apoptotic index [p 0.018] in the EBV + cancers when compared to EBV negative cancers. As reported in literature, strong negative correlation was noticed in the expression of Bcl-2 with A l and expression of BAX expression of BAX and A 1 were positively correlated in the cancer lesions. The results of the present study demonstrate a strong downregulation of apoptotic mechanism in nasopharyngeal carcinoma. The result suggest EBV infection to be partly responsible for the downregulation of apoptois, acting mainly by overexpressing Bcl-2 protein and tilting the Bcl-2BAX ratio to the advantage of cell survival. Thus these observations help to further define the links between EBV infection apoptosis associated proteins and nasopharyngeal cancer development