Expressions Of Matrix Metalloproteinase 9 And Interleukin 8 In Nasopharygeal Carcinoma And Relationship With Epstein-Barr Virus Latent Membrane Protein-1

Background: Nasopharyngeal carcinoma (NPC) characterized with infiltrating and metastasis is one of malignant tumor in head and neck. 90% NPC patients have been founded with neck lymphatic metastasis at their first examination. Studies have demonstrated the relationship between NPC and Epstein-Barr virus (EBV) infection. Latent membrane protein-1 (LMP1), expressed by EBV-DNA, is the primary carcinogen with multiple biological functions. Tumor metastasis is the result of multi-interaction between tumor cells and host cells. Newborn capillary blood vessels and basement membrane breakdown involved by tumor cells have a key role in tumor metastasis. Matrix metalloproteinase 9 (MMP9) is one of the representative substances that can degrade basement membrane and extracellular matrix. Interleukin-8 (IL-8) has been identified as an angiogenin, which play an important role in vascular formation in tumors. Previous studies had demonstrated that NPC can express MMP9. IL8 and LMP1 highly, but their association with clinical data and correlation between each other were not very clear. In our experiment, the expressions of MMP9, IL8 and LMP1 were immunohistochemical studied in 53 nasopharyngeal carcinoma sections. We statistically analyzed the correlation of these data and also the relationship between the clinical features and the experimental data of these patients. We wanted to evaluate the value of MMP9, IL8 and LMP1 in neck lymph nodes metastasis in nasopharyngeal carcinoma. We also wanted to know the correlation between LMP1 and MMP9, IL8 in nasopharyngeal carcinoma.Materials and Methods: We obtained 53 nasopharynx biopsy specimens from patients with nasopharyngeal carcinoma who had been diagnosed definitely by pathology in the first hospital of Wen Lin city from 2000-2005. The specimens included 29 male and 24 female patients (age ranged from 18 to 81 year old, mean age was 52 year). Neck lymph nodes metastasis in these patients was 38 cases, and none neck lymph nodes metastasis was 15 ones. Pathological classification: keratinizing squamous cell carcinoma was 4 cases, nonkeratinizing squamous cell carcinoma 27, and undifferentiated carcinoma 22. According to 97 UICC classification, T₁ was 14 cases, T₂14, T3 14 and T₄ 11; N₀ was 15 cases, N₁ 22, N₂ 11 and N₃ 5; Stage I was 5 cases, II 13, III 20 and IV 15. 10 nasopharyngeal biopsy specimens were collected from patients with chronic nasopharyngitis who had been diagnosed definitely by HE stain in the same hospital (male 6 and female 4), which were served as normal controls. All these tissue samples were fixed in 10% formaldehyde solution after being obtained, then embedded in paraffin, 5-micrometer thick sections were prepared for examining the expression of MMP9, IL8 and LMP1 by streptavidin-peroxidase immunochemistry. All the figures were analyzed statistically with SPSS 12.0 software in computer.Result: 1 Positive expression rate of MMP9 was 66.04%(35/53), mean positive score of MMP9 was 33.19 ± 29.73%; Positive expression rate of IL8 was 66.04%(35/53), mean positive score of IL8 was 33.46±30.23%; Positive expression rate of LMP1 was 66.04%(35/53), mean positive score of LMP1 was 35.49 + 29.63%.2 There were significant corelation of MMP9, IL8 and LMP1 with N stage (p<0.01). none-significant relation of MMP9, IL8 and LMP1 with age. gender, tumor stage, clinical stage and pathological classification (p>0.05).3 The expression of MMP9 showed a significant positive correlation with the expression of LMP1 ( γ =0.792, p<0.001) ;The expression of IL8 also showed a significant positive correlation with the expression of LMP1 ( γ=0.786, p<0.001) .Conclusion: The results suggested that MMP9, IL8 and LMP1 were highly expressed in nasopharyngeal carcinoma cells, and the expressions of MMP9, IL8 and LMP1 were significantly associated with ncek lymph nodes metastasis. The expression of LMP1 showed a significant positive correlation with the expression of MMP9 and IL8, and it showed that LMP1 could enhance NPC metastasis by up-regulating the expression of MMP9 and IL8.