大鼠实验性肺鳞癌癌变各阶段环氧化酶-2表达及微血管密度的动态研究

A Study on Cyclooxygenase-2 Protein Expression and Vasculature during Experimental Rat Lung Carcinogenesis

背景与目的:近期研究表明,环氧化酶-2(COX-2)参与了肿瘤的发生与发展,在多种肿瘤组织中已检测到COX-2高表达,但它在癌前病变、转移癌中的表达报道较少,在体内它与肿瘤血管生成的关系也尚待证实。本研究检测COX-2在大鼠肺鳞癌癌变进展各阶段病变组织中的表达,探讨COX-2表达与微血管密度(MVD)的关系及应用抑制COX-2表达的非甾体类抗炎药防治肺鳞癌的可能性。方法:Wistar大鼠90只,实验组80只左肺叶支气管灌注致癌质碘油,分批处死获取肺鳞癌癌变及进展各阶段病变标本,对照组10只左肺叶支气管灌注碘油。应用免疫组化检测癌变及进展各阶段病变组织中及10例正常对照组织中COX-2表达,结合COX-2阳性细胞百分比及阳性细胞染色强弱两个方面计算COX-2免疫组化染色评分。在VonWillebrandfactor免疫组化染色切片上计数MVD。结果:共获取肺鳞癌癌变及进展各阶段病变标本147例:支气管粘膜增生14例,鳞状化生25例,不典型增生33例,原位癌12例,浸润癌54例,转移癌9例。不典型增生COX-2表达评分(2.1±1.9)与鳞状化生(0.6±0.9)相比,原位癌(3.7±2.4)与不典型增生相比,转移癌(5.6±3.6)与浸润癌(3.9±2.7)相比,评分增高,差异有显著性意义(P值依次为<0.01,<0.05,<0.05)。原位癌MVD值(31.7±13.3)与不典型增生(6.2±4.0)相比,浸润?

Background &Objective:There is evidence that cyclooxygenase 2(COX 2) involved in the occurrence and development of neoplasms. Elevated expression of COX 2 in carcinomas and antitumor effects of nonsteroidal antiinflammatory drug(COX 2 inhibitors) have been reported, but COX 2 expression in precancerous lesions and its association with angiogenesis is not clearly defined. The aim of this study was to investigate the expression of COX 2 protein and its association with microvessel density (MVD) during the experimental rat lung carcinogenesis. Methods: Eighty Wistar rats were intra leftlobar bronchial instilled with 3 methylcholanthrene and diethylinitrosamine to induce lung squamous cell carcinoma, and ten rats were instilled lipiodol as control group. To acquire every pathological phase during the carcinogenesis, rats were sacrificed at intervals from fifteen days to nine months. COX 2 expression and MVD count in the samples of every pathological phase during the carcinogenesis were examined by immunohistochemistry. The immunohistochemical score of COX 2 was calculated by combining an estimate of the percentage of immunoreactive cells with an estimate of the staining intensity. Inter tumor MVD was marked by anti Von Willebrand factor monoantibody. Results: One hundred and forty seven specimens of every pathological phase during the carcinogenesis were obtained which including fourteen hyperplasia, twenty five squamous metaplasia, thirty three dysplasia, twelve carcinoma in situ, fifty four infiltration carcinoma, nine metastasis. The expression of COX 2 and MVD count increased during rat lung carcinogenesis. COX 2 immunohistochemical score was significantly higher in dysplasia, carcinoma in situ and metastasis(P< 0 01,P< 0 05,P< 0 05 respectively), and significant increased MVD were found in carcinoma in situ, infiltration carcinoma and metastasis(P< 0 01). During cacinogenesis, there was a significant correlation between COX 2 expression and MVD(r=0.9521,P< 0 001, b=11 51). Conclusion:COX 2 may play an important role during the carcinogenesis in experimental rat lung squamous cell carcinoma as well as its metastasis, partly by stimulating angiogenesis.