人卵巢上皮癌裸鼠原位移植瘤癌旁肿瘤相关基因表达及意义

Expressions and significance of tumor associated genes in tissues adjacent to human epithelial ovari an cancer of orthotopic implantation in nude mice

目的通过对人卵巢上皮癌裸鼠原位移植瘤癌旁肿瘤相关基因表达的检测，探讨筛选癌旁正常卵巢组织的可行性。方法人卵巢上皮癌OVCAR3细胞皮下种植获取瘤源并卵巢原位移植后，取癌组织、癌旁近端组织、癌旁中段组织、癌旁远端组织及正常裸鼠卵巢组织，采用免疫组化法检测以上组织的CKG、CA125、P53、survivin、MMP-2、T1MP-2的表达量。结果40例人卵巢上皮癌裸鼠原位移植瘤模型中获取35份活检正常的癌旁残余卵巢组织，获取率87．5％（35／40）。癌组织中cK．7、CA125、P=53、suivin、MMP4及TIMP-2的表达率分别为95．O％（38／40）、95．0％（38／40）、75．0％（30／40）、85．0％（34／40）、77．5％（31／40）及77．5％（31／40）；癌旁近端组织的表达率分别为71．4％（25／35）、68．6％（24／35）、57．1％（20／35）、62．9％（22／35）、60．0％（21／35）及57．1％（20／35）；癌旁中段组织的表达率分别为34．3％（12／35）、31．4％（11／35）、31．4％（11／35）、31．4％（11／35）、34．3％（12／35）及31．4％（11／35）；癌旁远端组织的表达率分别为25．7％（9／35）、22．9％（8／35）、25．7％（9／35）、25．7％（9／35）、28．6％（10／35）及31．4％（11／35）；23份癌旁正常卵巢组织CK．7、CAl25、P53、suivin、MMP4及ⅡMP-2的表达均为阴性。免疫组化检测结果为癌旁近端组织中cK-7、CAl25、P=53、suivin、MMP-2及TIMP-2的表达低于癌组织（P〈0．05），高于癌旁中段组织及癌旁远端组织（P〈0．01）；癌旁中段组织及癌旁远端组织表达差异无统计学意义（P〉0．05）；cK-7、CAl25、suivin的强阳性表达率明显高于P53、MMP4、11MP-2（P〈0．01）；不同病变程度获取的癌旁正常卵巢组织中的表达量差异无统计学意义（P〉0．05）。20例正常裸鼠卵巢组织CK-7、CAl25、P53、suivin、MMP4、TIMP-2的表达均为阴性。结论CKG、CAl25、P53、suivin、MMP-2及11MP-2等分子指标的表达向无癌方向呈递减趋势，其肿瘤相关基因表达阴性可作为筛选癌旁残余正常卵巢组织的标准，卵巢上皮癌旁可以获取相对安全的正常卵巢组织。

Objective To investigate the feasibility in screening of normal ovarian tissues by evalu ating the expressions of tumor associated genes in tissues adjacent to human epithelial ovarian cancer of or thotopic implantation in nude mice. Methods Human epithelial ovarian cancer cell lines OVCAR3 were grown in subcutaneous tissues, and the tumor tissues were orthotopic implanted. The expressions of CK7, CA125 ,P53, survivin, MMP2, and TIMP2 were detected by immunohistochemical staining in proximal tis sues, middle tissues, distal tissues adjacent to tumor, tumor tissues, and normal ovarian tissues of nude mice. Results 35 samples ovarian tissues with normal biopsy were gained from 40 cases of human epitheli al ovarian cancers of orthotopic implantation model in nude mice. The expression rate of CK7, CA125, P53,survivin, MMP2, and TIMP2 were 95.0% （38/40）, 95.0% （38/40） , 75.0% （30/40）, 85.0% （34/ 40）, 77.5% （31/40） , and 77.5% （31/40） in tumor tissues, respectively; 71.4% （25/35）, 68.6% （24/35）, 57.1% （20/35）, 62. 9% （22/35）, 60. 0% （21/35）, and 57.1% （20/35） in proximal tissues adjacent to tumor, respectively; 34. 3% （ 12/35 ）, 31.4% （ 11/35 ）, 31.4% （ 11/35）, 31.4% （ 11/35 ）, 34. 3% （ 12/35）, and 31.4% （11/35） in middle tissues adjacent to tumor, respectively; and 25.7% （9/ 35）, 22.9% （8/35）, 25. 7% （9/35）, 25.7% （9/35）, 28.6% （ 10/35 ）, and 31.4% （11/35） in distal tissues adjacent to tumor, re respectively. The expressions of CK7, CA125, P53, survivin, MMP2 , and TIMP2 were all negative in 23 samples normal ovarian tissues adjacent to tumor. The expressions of CK7, CA125, P53, survivin, MMP2 and TIMP2 in proximal tissues adjacent to tumor were lower than those in tumor tissues（ P 〈 0.05）, and higher than those in middle tissues and in distal tissues adjacent to tumor（ P 〈 0. 01 ）. There were no expression difference between in middle tissues and in distal tissues （ P 〉 0. 05）. The strong positive expressions of CK7, CA125, and survivin were higher than those of P53, MMP2, and TIMP2 （ P 〈 0. 01 ）. No significant difference was found in those expressions in the normal ovarian tissues adjacent to tumor gained from orthotopic implantation model with different severity. The ex pressions of CK7, CA125, P53, survivin, MMP2, and TIMP2 were all negative in 20 normal ovarian tis sues of nude mice. Conclusions The expression of CK7, CA125, P53, survivin, MMP2, and TIMP2 showed decreasing trend to noncancer direction. Negative expressions of these tumor associated genes can be used as standard in screening of normal ovarian tissues adjacent to tumor. Relative safe normal ovarian tissues can be obtained from the tissues adjacent to tumor.