高危型人乳头瘤病毒感染后Topo Ⅱα和p16INK4A蛋白的表达及诊断价值

The expression of Topoisomerase Ⅱ and p16INK4A in cervical intraepithelial neoplasia after infection of high-risk type human papillomavirus and their value for diagnosis

目的探讨高危型人乳头瘤病毒(HR-HPV)感染后Topo Ⅱα和p16INK4A在宫颈组织中的表达及其对癌前病变的诊断价值。方法选取在温州医学院附属二院行宫颈病变诊治的患者135例,包括各级宫颈上皮内瘤变(CIN)和宫颈鳞癌(SCC)的患者。随机选取同期就诊的慢性宫颈炎患者30例作为对照。运用第二代杂交捕获法(HC2)检测高危型人乳头瘤病毒(HR-HPV)的表达。活体提取组织,运用免疫组织化学法(SP法)检测宫颈组织中Topo Ⅱα和p16INK4A蛋白表达。结果在HR-HPV阳性患者的宫颈组织中Topo IIα和p16INK4A表达率高于HR-HPV阴性患者,差异有统计学意义。Topo Ⅱα和p16INK4A在正常宫颈上皮组织、各级CIN和SCC中的表达率逐渐增加,差异有统计学意义。p16INK4A用于筛查宫颈癌前病变(包括SCC)时阳性预测值99.3%。Topo Ⅱα用于筛查宫颈严重病变(CINⅢ和SCC)时阳性预测值67.9%。结论 HR-HPV感染后Topo Ⅱα和p16INK4A蛋白表达明显增高,并且Topo IIα和p16INK4A蛋白表达率随着宫颈癌前病变的严重程度而上调,参与宫颈上皮的异常增殖和恶性转变。p16INK4A免疫组化检测提高了宫颈癌前病变筛查的特异性,Topo Ⅱα免疫组化检测提高了宫颈严重病变筛查的特异性,当Topo Ⅱα蛋白表达阳性,宫颈组织可能已发生不可逆性病变。

Objective To investigate the expression of Topoisomerase Ⅱ and p16INK4A in cervical intraepithelial neoplasia（CIN） and invasive squamous cell carcinoma（SCC） after infection of HR-HPV,and attempt to provide the basis for earlier diagnosis of cervical cancer.Methods 135 patients with CIN or SCC were enrolled in the Second Affiliated Hospital of Wenzhou Medical College.Another 30 patients during the same period with chronic cervictits were selected as the control group.Hybird capture Ⅱ assay（HC2） was used to detect the expression of HR-HPV of all the patients.All tissues were diagnosed and grouped through HE after operation.Immunohistochemical staining（SP） was used to detect the Topoisomerase Ⅱ and p16INK4A in these tissues.Results The positive rates of expression of Topoisomerase Ⅱ and p16INK4A were increased in HR-HPV-positive lesions than that in HR-HPV-negative ones（P0.05）.The positive rates of expression of Topoisomerase II and p16INK4A in NCE,CIN I,CIN II,CIN III and SCC were increased along with the grade of the lesion（P0.05）.Positive predictive value for p16INK4A as the marker of CIN（including SCC） were 99.3%,while that for Topoisomerase Ⅱ as the marker of serious cervical lesion（CIN Ⅲ and SCC） were 67.9%.Conclusion Topoisomerase Ⅱ and p16INK4A expressions were up-regulated after infection of HR-HPV along with the increasing grade of cervical lesion,and could involved in abnormal proliferation and cancerization of cervix epithelium.As a marker,p16INK4A expression could enhance the specificity for CIN screening.Topoisomerase Ⅱ expression could help to determine the grade of CIN,and enhance the specificity for serious cervical lesion（CIN Ⅲ and SCC）.