Association Between MMP9 And EBV Infection With Metastasis In Nasopharyngeal Carcinoma

Backround: Nasopharyngeal carcinoma (NPC) characterized with neck lymph nodes and distant organs metastasis is the most common one of tumors in head and neck. Previous studies had demonstrated the association between NPC and Epstein-Barr virus (EBV) infection. Matrix metalloproteinases (MMPs), a gene family of Zinc-containing endopeptidase, degrade extracellular matrix and play an essential role in the metastasis process. Among MMP families, Matrix metalloproteinase 9 (the 92-lcD type collagenase/ gelatinaes B) which selectively degrades type IV collagen, major component of extracellular matrix, was reported to be markedly associated with metastasis of many kinds of tumor cells. We examined the expression of MMP9 by immunochemistry and EB virus encoded small nuclear mRNA (EBER) by in situ hybridization, and statistically analyzed the relation of them. We also analyzed the association of MMP9 with clinical features. We wanted to evaluate the expression of Matrix metalloproteinase-9 in nasopharyngeal carcinoma and the association between MMP9 and EBV infection.Materials and Methods: We obtained 41 nasopharynx biopsy specimens from patients with nasopharyngeal carcinoma who got treatment in Sir Run Run Shaw hospital from 1998-2002, among whom well-differentiated squamous cell carcinoma was 1 case, moderate-differentiated squamous cell carcinoma 11 ones, low-differentiated squamous cell carcinoma 16 and undifferentiated carcinoma 13. The specimens included 26 male patients and 15 female patients (age ranged from 29 to 74 year old, mean age was 54.73 year). According to UICC classification, T1 was 7 cases, T2 21, T3 8 and T45; N0 was 9 cases, N, 11, N215 and N3 6; Stage I was 1 case, 115, HI 12 and IV 23. All the 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 by Streptavidin-peroxidase immunochemistry and EBER by in situ hybridization. All thefigures were analyzed statistically with SPSS 10.0 software in computer.Result: 1. Positive expression rate of MMP9 was 73.17%, and that of EBER was 97.56%; mean positive score of MMP9 was 46.32% ±33. 33%, and that of EBER was 69. 32% ± 19. 19%2. There was significant association of MMP9 with N stage and clinical stage (p<0.0001), none-significant relation of MMP9 with age, gender, tumor stage and pathological classification (p>0.05). There was also no relation between EBER and age, gender, T stage, N stage, pathological classification and clinical stage (p>0.05).3. The expression of MMP9 showed a significant positive correlation with the expression of EBER (y =0.483, p=0.001).Conclusion: The result suggests that MMP9 and EBV infection are highly expressed in nasopharyngeal carcinoma cells and the expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus infection is positively correlated with the expression of MMP9, and it shows that EB virus can enhance NPC metastasis by up-regulating the expression of MMP9.