宫颈上皮内肿瘤组织β-连结蛋白表达和分布特点及其意义的研究

Expression and cellular distribution of β-catenin in cervical intraepithelial neoplasia and its significance

目的:探讨宫颈上皮内肿瘤(cervical intraepithelial neoplasia,CIN)组织β-连结蛋白(β-catenin,β-cat)表达和分布特点及在宫颈癌发生中的作用。方法:采用免疫组化检测20例正常宫颈鳞状上皮、193例CIN(Ⅰ级60例,Ⅱ级57例,Ⅲ级76例)及20例浸润癌组织β-cat和细胞周期素D1(Cyclin D1)的表达。结果:正常宫颈上皮β-cat主要表达于基底层及副基底层的上皮细胞胞膜上,CIN和浸润癌β-cat则显示明显的胞质着色或异质性着色或无着色,但所有病例均未见胞核着色;CINⅠ、Ⅱ、Ⅲ级和浸润癌β-cat异常表达率与正常组比较均显著性升高,χ2值分别为9.492、15.439、29.856和29.565,P值分别为0.002、0.000、0.000和0.000。高级别CINβ-cat异常表达率亦显著高于低级别者,χ2=10.484,P=0.001。正常宫颈上皮仅在基底层及副基底层细胞的胞核内可见散在Cyclin D1阳性着色,CIN和浸润癌Cy-clin D1多呈阴性表达或表达下调,仅少数病例表达上调,总上调率为5.6%(12/213);CINⅠ、Ⅱ、Ⅲ级和浸润癌与正常组比较,Cyclin D1表达上调率差异均无统计学意义,χ2值分别为0.351、0.001、0.176和0.526,P值分别为0.554、0.975、0.675和0.468。相关分析显示,213例宫颈各病变组织β-cat异常表达与Cyc-lin D1上调表达无相关性,r=0.096,P=0.161。结论:β-cat表达和分布的异常在CIN和浸润癌是常见的改变,可能与CIN发生和病变进展(尤其是从低级别向高级别进展和恶性转化)过程密切相关。

OBJECTIVE： To investigate the expression and cellular distribution of β-catenin in cervical intraepithelial neoplasia （CIN） and its possible role in carcinogenesis of human cervical carcinoma. METHODS： The expression and cellular distribution of β-catenin and Cyclin D1 were detected by the immunohistochemical staining in biopsy samples from 20 normal exocervical squamous epithelium, 193 CIN （60 CIN1, 57 CIN2 and 76 CIN3） and 20 infiltrative squamous cell carcinomas （ISCCs）. RESULTS： In normal cervical epithelium, β-catenin was mainly observed in all cases at the plasma membrane of both basal and parabasal cells, while CIN1, 2, 3 and ISCCs exhibited markedly cytoplasmic or heterogeneous or negative staining of β-catenin but, all no nuclear staining and the frequency of abnormal β-catenin expression significantly increased when compared with that of the normal controls Х^2 values were 9. 492, 15.439, 29.856, 29.565, P values were 0.002, 0.000, 0.000, 0,000, respectively）. Statistical significance was also seen between high grade CIN and low grade （Х^2 = 10. 484, P=0. 001）. Cyclin D1 positive stai ning was only observed at a few nuclei of both basal and parabasal cells in normal cervical epithelium. The negative or low expression of Cyclin D1 was frequently seen in CIN and ISCCs, the total rates of overexpression was only 5. 6%（12/213） and no statistical significance was found between the lesions and the normal controls （CIN1, 2, 3 and ISCCs vs the normal control： Х^2 values were 0.351, 0.001, 0. 176, 0.526, P values were 0. 554, 0. 975, 0. 675, 0. 468, respectively）. In 213 various cervical lesions including CIN and IS：12Cs, the abnormal β-catenin expression had no correlation with the overexpression of Cyclin D1 （r= 0. 096, P = 0. 161）.CONCLUSION： The abnormal expression and cellular distribution of β-catenin are frequently seen in CIN and ISCCs, which is in high correlation with tumorigenesis and progression of CIN, especially involving the process transforming from low grade CIN to high grade and to malignance.