间隙连接蛋白表达与宫颈原位癌生长发展的相关性研究

Correlation of Expression of Connexin to Growth and Progression of Cervical Carcinoma In Situ

背景与目的:原位癌中间隙连接蛋白(connexin,CX)介导的细胞间隙连接通讯(gap junction intercellular com m unication,GJIC)是相邻细胞之间直接通讯的惟一方式,CX表达的变化以及GJIC功能的改变可能在宫颈组织癌变过程中起一定的作用并对原位癌发生发展有重要影响。本研究旨在检测宫颈正常鳞状上皮、不典型增生上皮、原位癌和浸润性鳞癌这个连续癌变模式中CX m RNA和蛋白质表达的变化,并探讨CX表达的变化与宫颈原位癌发生、发展的相关性。方法:采用免疫组化和原位杂交技术检测30例宫颈原位癌石蜡切片中CX43和CX26m RNA和蛋白质表达情况,采用免疫组化检测Ki-67蛋白的表达,并以宫颈30例正常鳞状上皮、22例不典型增生上皮和26例浸润性鳞癌为对照。结果:(1)在正常鳞状上皮、不典型增生上皮、原位癌和浸润性鳞癌中,CX43蛋白质阳性率依次为83%、55%、50%、30%;CX43m RNA阳性率依次为97%、64%、58%、46%;CX26m RNA阳性率依次为93%、68%、55%、42%;可以看出CX43(m RNA、蛋白质)和CX26(m RNA)阳性率逐渐降低。原位癌组CX阳性率明显低于正常鳞状上皮组,两组之间差异有显著性(P<0.05);原位癌组内,CX表达以弱阳性为主,阳性程度明显低于正常鳞状上皮;原位癌与正常鳞状上皮直接相邻区域,CX表达是明显减弱或消失的。(2)

BACKGROUND & OBJECTIVE: Gap junction intercellular communication (GJIC), mediated by connexin (CX), is the unique type of intercellular communication in carcinoma in situ (CIS). Changes in expression of CXs and function of GJIC may play roles in carcinogenesis of cervical cancer and progression of CIS. This study was to investigate the expression of CXs in normal epithelium (NE), hyperplasia, CIS, and invasive carcinoma (IC) of cervix, to explore correlation of expression of CXs to pathogenesis and progression of cervical CIS. METHODS: Expression of CX43 (mRNA, protein), CX26 (mRNA), and Ki-67 (protein) in 30 specimens of cervical NE, 22 specimens of cervical hyperplasia, 30 specimens of cervical CIS, and 26 specimens of cervical IC were detected by immunohistochemistry and in situ hybridization. RESULTS: In cervical NE, hyperplasia, CIS, and IC, positive rates of CX43 protein were 83%, 55%, 50%, and 30%, respectively, and positive rates of CX43 mRNA were 97%, 64%, 58%, and 46%, respectively; positive rates of CX26 mRNA was 93%, 68%, 55%, and 42%, respectively. Positive rates of CX43 (mRNA, protein) and CX26 (mRNA) were gradually decreased. Positive rate of CX was significantly lower in CIS group than in NE group (P < 0.05). The expressions of CX26 and CX43 were weaker in CIS group than in NE group; their expressions were obviously decreased, or even vanished in the area of CIS adjacent to NE. Proliferating index (PI), indicated by expression of Ki-67 protein, was increased gradually in NE (5%), hyperplasia (12%), CIS (30%), and IC (62%); the differences were significant (P < 0.05) between CIS group and other groups. CONCLUSIONS: CX26 and CX43 may play important roles in carcinogenesis of cervical cancer. CXs may inhibit tumorigenesis and cell proliferation; it might be key factors in earlier stages when cellular malignant phenotypes have been established, or NE has been transformed into CIS.