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

Abstract

Objective To investigate the feasibility in screening of normal ovarian tissues by evaluating the expressions of tumor-associated genes in tissues adjacent to human epithelial ovarian cancer of orthotopic 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 CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were detected by immunohistochemical staining in proximal tissues,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 epithelial ovarian cancers of orthotopic implantation model in nude mice.The expression rate of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 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 CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were all negative in 23 samples normal ovarian tissues adjacent to tumor.The expressions of CK-7,CA125,P53,survivin,MMP-2 and TIMP-2 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 CK-7,CA125,and survivin were higher than those of P53,MMP-2,and TIMP-2 (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 expressions of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were all negative in 20 normal ovarian tissues of nude mice.Conclusions The expression of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 showed decreasing trend to non-cancer 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. Key words: Ovarian neoplasms/genetics; Ovarian neoplasms/pathology; Gene expression; Disease models, animal ; Mice, nude ; Neoplasm transplantation