Cx43、Skp2在卵巢上皮性肿瘤组织中的表达及临床意义

Expressions of Cx43 and Skp2 in Epithelial Ovarian Tumor and Their Clinical Significances

背景与目的:间隙连接蛋白43(connexin43,Cx43)是间隙连接蛋白家族的主要成员,在多种肿瘤细胞中表达下降。它在许多细胞系以依赖间隙连接(Gapjunction)的途径发挥抑癌作用。最近研究发现它还可能通过抑制S期激酶相关蛋白2(S-phase kinase associated protein2,Skp2)的表达而起到抑制肿瘤生长的作用。Skp2是F鄄box蛋白家族的成员,它能特异性识别并促进某些调节G1期进程的关键性细胞周期调节物的降解,在许多肿瘤中表达升高。本研究检测Cx43和Skp2在卵巢上皮性肿瘤中的表达,探讨它们的表达与卵巢癌发展的关系,以及这两种蛋白表达的相互关系。方法:收集81例卵巢上皮性肿瘤的外科手术石蜡标本(良性13例、交界性12例、恶性56例),用免疫组化的方法检测Cx43和Skp2蛋白的表达水平。分析它们的表达水平与临床病理参数的关系以及二者的相互关系。结果:Cx43蛋白在卵巢上皮性良性、交界性及恶性肿瘤中阳性率分别为84.6%、66.7%和33.9%,经免疫组化半定量分析,其在上皮性卵巢癌中的表达水平明显低于良性肿瘤(P<0.01)和交界性肿瘤(P<0.01),在不同年龄及组织类型的卵巢癌中表达无显著性差异(P>0.05),而在中低度分化组、Ⅲ～Ⅳ期组及有淋巴结转移组分别明显低于高分化组(P<0.05)、Ⅰ～Ⅱ期组(P<0.05)及无淋巴结转移组(P<0.

BACKGROUND & OBJECTIVE: Connexin 43 (Cx43), an important member of connexins family, is frequently down-regulated in neoplastic cells. It has been shown to have gap junction-dependent anti-tumor effect on various tumor cell lines. Recently, it was reported that Cx43 could inhibit tumor growth via down-regulating the expression of S-phase kinase associated protein 2 (Skp2). Skp2, a member of F-box protein family, can specifically recognize, and accelerate the ubiquitin-mediated degradation of several key regulators of G1 phase progression. This study was to detect expressions of Cx43 and Skp2 in epithelial ovarian tumor, and to explore their correlations to tumorigenesis and development of ovarian cancer. METHODS: Expressions of Cx43 and Skp2 were examined by immunohistochemistry in 81 specimens of epithelial ovarian tumor (13 specimens of adenoma, 12 specimens of borderline adenoma, and 56 specimens of adenocarcinoma). Relationship between expression levels of Cx43 and Skp2, and association of their expression levels with clinicopathologic factors were statistically analyzed. RESULTS: Positive rates of Cx43 in ovarian adenoma, borderline adenoma, and ovarian adenocarcinoma were 84.6% (11/13), 66.7% (8/12), and 33.9% (19/56), respectively; expression level of Cx43 in ovarian adenocarcinoma was significantly lower than those in ovarian adenoma (P<0.01), and borderline adenoma (P<0.01). Positive rates of Skp2 in ovarian adenoma, borderline adenoma, and ovarian adenocarcinoma were 0, 0, and 46.3% (26/56), respectively; expression level of Skp2 in ovarian adenocarcinoma was significantly higher than those in ovarian adenoma (P<0.01), and borderline adenoma (P<0.01). Moreover, the expression levels of Cx43 and Skp2 were independent of age and histological type, but significantly associated with pathologic grade, clinical stage, and positive lymph node metastasis of ovarian adenocarcinoma. Besides, in ovarian adenocarcinoma, expression level of Cx43 was moderately inversely correlated with that of Skp2 (r=-0.48, P<0.01). CONCLUSIONS: Down-regulation of Cx43, and over-expression of Skp2 are tumor specific, and may play important roles in tumorigenesis, and development of ovarian cancer. Up-regulation of Skp2 may be related with down-regulation of Cx43 in ovarian cancer.