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

Abstract

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.

It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer

“…These data are valuable because identification of early cellular changes in NPC pathogenesis may serve clinicians in early identification for disease and/or in guiding treatment. One study found that higher levels of LMP1 were associated with larger tumor size and poorer 5-year survival [160]. Others have identified EBV DNA, and downstream effects of viral proteins (such as markers of oxidative stress, RIP3 hypermethylation) to be informative prognostic indicators [161].…”

Immunohistochemical diagnosis of human infectious diseases: a review

“…Immunohistochemistry identified EBV latent membrane protein 1 using tissue sections in apical and periapical periodontitis lesions (Fig. 5 B) [ 115 , 116 ], in patients with nasopharyngeal carcinoma [ 117 ], in immunocompetent adult [ 118 ], and in Hodgkin's disease and non-Hodgkin's lymphoma [ 119 – 121 ].…”

It Takes Two to Tango; A Review of Oncogenic Virus and Host Microbiome Associated Inflammation on Head and Neck Cancer

“…These data are valuable because identification of early cellular changes in NPC pathogenesis may serve clinicians in early identification for disease and/or in guiding treatment. One study found that higher levels of LMP1 was associated with larger tumor size and poorer 5-year survival [141]. Others have identified EBV DNA, and downstream effects of viral proteins (such as markers of oxidative stress, RIP3 hypermethylation) to be informative prognostic indicators [142].…”