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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 Topo Ⅱα and p16INK4A in cervical tissues after high-risk human papillomavirus (HR-HPV) infection and its value in the diagnosis of precancerous lesions. Methods A total of 135 patients with cervical lesions diagnosed and treated in the Second Affiliated Hospital of Wenzhou Medical College were enrolled in the study. They included all patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC). Thirty patients with chronic cervicitis randomly selected during the same period were selected as control. The second generation hybridization capture method (HC2) was used to detect the expression of high-risk human papillomavirus (HR-HPV). Tissues were extracted from living tissues and the expression of Topo Ⅱα and p16INK4A protein in cervical tissues was detected by immunohistochemistry (SP method). Results The positive rates of Topo IIα and p16INK4A in HR-HPV positive patients were higher than those in HR-HPV negative patients, the difference was statistically significant. Topo Ⅱα and p16INK4A expression in normal cervical epithelium, CIN and SCC at all levels gradually increased, the difference was statistically significant. p16INK4A was used to screen 99.3% of the positive predictive value of cervical precancerous lesions (including SCC). The positive predictive value of Topo Ⅱα in screening severe cervical lesions (CIN Ⅲ and SCC) was 67.9%. Conclusion The expression of Topo Ⅱ a and p16 INK4A protein were significantly increased after HR-HPV infection, and the expression rates of Topo IIα and p16INK4A protein were up-regulated with the severity of cervical precancerous lesions, and were involved in the abnormal proliferation and malignant transformation of cervical epithelium. Immunohistochemical detection of p16INK4A increased the specificity of screening of precancerous lesions of cervical cancer. Topo Ⅱ α immunohistochemistry detection enhanced the specificity of screening of severe cervical lesions. When Topo Ⅱα protein expression is positive, cervical tissue may have irreversible lesions.