The Clinical Significance of IGF-1R and Relationship with Epstein-Barr Virus Markers: LMP1 and EBERs in Tunisian Patients with Nasopharyngeal Carcinoma.

OBJECTIVES: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein-Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. METHODS: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. RESULTS: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size (P < .001). Kaplan-Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression (P = .018). The relationship between these two biomarkers could influence patient survival. CONCLUSION: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.

Complementary determination of Epstein-Barr virus DNA load and serum markers for nasopharyngeal carcinoma screening and early detection in individuals at risk in Tunisia.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.