外阴鳞状细胞癌中人乳头状瘤病毒感染与基质金属蛋白酶9和金属蛋白酶抑制剂1的关系

HPV Infection and its Correlation with MMP-9 and TIMP-1 Expression in Vulvar Squamous Cell Carcinoma

目的探讨人乳头状瘤病毒(HPV)6/11、16/18在外阴鳞状细胞癌(简称外阴鳞癌)组织中的感染情况及与基质金属蛋白酶9(MMP-9)和金属蛋白酶抑制剂1(TIMP-1)蛋白表达的关系。方法用原位杂交法检测HPV6/11、16/18在26例外阴鳞癌、21例外阴上皮内瘤病变(VIN)及10例外阴正常皮肤组织中的感染情况。同时用免疫组化法检测MMP-9、TIMP-1蛋白的表达。结果HPV6/11、16/18在外阴鳞癌、VIN中的感染率分别为69.23%(18/26)和38.46%(10/26),42.86%(9/21)和28.57%(6/21),正常对照组没有感染。MMP-9、TIMP-1蛋白在外阴鳞癌、VIN、正常对照组中的阳性表达率分别为92.31%(24/26)和76.92%(20/26),90.48%(19/21)和80.95%(17/21),80.00%(8/10)和50.00%(5/10)。HPV6/11的外阴鳞癌组、VIN组与正常对照组比较差异有显著性(P<0.05),HPV16/18的外阴鳞癌组与正常对照组比较差异有显著性。外阴病变各组MMP-9、TIMP-1阳性表达率与正常对照组比较差异均有显著性。在外阴鳞癌中MMP-9蛋白表达较TIMP-1蛋白表达强(P<0.05)。MMP-9在有HPV6/11和HPV16/18感染患者中的表达较无感染者强,而TIMP-1蛋白的表达差异无显著性。结论在外阴鳞癌的发生发展中HPV的感染起一定作用,当MMP-9的表达强于TIMP-1表达时可能是外阴鳞癌侵袭的一个指标。

Objectives To investigate HPV infection and its correlati on with the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibito r of metalloproteinase-1 (TIMP-1) in vulvar squamous cell carcinoma (VSCC). Meth ods HPV6/11 and 16/18 DNA were detected using in situ hybridization in 26 case s of VSCC, 21 cases of vulvar intraepithelial neoplasia (VIN) and 10 specimens o f normal skin. The expression of MMP-9 and TIMP-1 was measured by immunohistoche mical method in these three groups. Results The infection rates of HPV6/11 and 16/18 in VSCC and VIN were 69.23% (18/26) and 38.46% (10/26), 42.86% (9/21) and 28.57% (6/21) respectively, and no HPV6/11 or 16/18 DNA was discovered in norma l skin epidermis. The expression rates of MMP-9 and TIMP-1 in VSCC, VIN and norm al skin epidermis were 92.31%(24/26) and 76.92% (20/26), 90.45% (19/21) and 80.9 5% (17/21), and 80.00% (8/10) and 50.00% (5/10) respectively. MMP-9 expression in HPV positive lesions was higher than that in HPV negative lesions, but no sig nificant difference of TIMP-1 expression was observed in HPV positive and negati ve lesions. Conclusions HPV infection may play a role in the development of VS CC. The higher expression of MMP-9 comparing with that of TIMP-1 may be an early marker of tumor progression in VSCC, and HPV infection may facilitate the invas ion and metastasis of VSCC.