联合应用P16和Ki-67免疫组化染色对CIN分级诊断的影响及其与宫颈HPV感染的相关性

The impact the application of P16 and Ki67 immumohistochemical staining to the diagnosis of CIN and its relationship with HPV infection

目的探究不同CIN分级诊断中联合应用P16、Ki-67免疫组化染色的表达情况及P16的表达与宫颈HPV感染的关系。方法选取2013年6月至2014年6月期间本院妇科门诊经宫颈液基薄层细胞学检查(TCT)诊断ASCS及以上的200例患者作为研究对象根据患者的常规HE染色病理诊断将其分为宫颈慢性炎症组(112例)、CINⅠ组(42例)、CINⅡ组(20例)、CINⅢ组(18例,包括CINⅡ～Ⅲ级)以及宫颈癌组(8例)。采用HPV分型检测和宫颈阴道镜活检检测所有患者,联合应用P16、Ki-67免疫组化染色病变最严重的组织后进行半定量评分,并对宫颈病变进行病理诊断分级。结果 P16和Ki-67的阳性表达与患者宫颈病变级别有关:在宫颈慢性炎症组、CINⅠ组、CINⅡ组、CINⅢ组以及宫颈癌组中,P16的阳性表达率分别为0、71.43%、100%、100%、100%,而Ki-67的阳性表达率分别为0、49.05%、100%、100%、100%,且随着宫颈CIN病变程度越高,P16和Ki-67的阳性表达程度越强,差异有统计学意义(c2=156.012,152.727,P<0.001)。对比P16和Ki-67的免疫组化半定量评分评定的病理诊断分级和常规HE病理诊断分级,宫颈慢性炎患者的诊断一致率为100%,CIN患者的诊断一致率为95.45%。所有患者中HPV的感染率为67.50%,且HPV感染率随着P16表达强度升高而增高:-(57.26%),+(78.57%),++(81.48%),+++(88.00%),++++(90.00%),且P16表达阳性和阴性的患者中HPV-16型、HPV-58型、HPV-52型、HPV-31型、HPV-66型和高危混合型的感染率的比较差异有统计学意义(c2=4.295,5.327,8.807,13.831,17.273,11.489,P<0.05)。结论联合应用P16和Ki-67免疫组化染色半定量评分对CIN病变的分级预测具有较高的灵敏度和特异度,且对P16表达的检测能准确提示宫颈CIN病变合并HPV感染的预后和转归情况,在HPV感染的防治过程中应着重注意防治HPV-16型、HPV-58型以及HPV-18型感染。

Objective To explore the expression of the combined application of P16, Ki-67 immunohistochemical staining in the diagnosis of CIN and the relationship between P16 and HPV infection. Methods 200 patients with the diagnosis of ASCS and above by TCT in Outpatient Department of our hospital during June 2013 to June 2014 were chosen as research sample. Diagnosed them by HE staining pathological: 112 cases were divided into chronic cervical inflammation group, 42 cases were CIN I group, 20 cases were CIN II group, 18 cases were CIN III group (included CIN II^III) and 8 cases were cervical cancer group. HPV types detection and the cervical colposcopy biopsy were used to test all of the patients, combined the application of P16, Ki-67 immunohistochemical staining on the the worst organization lesions and then calculated its semi-quantitative Score, and made the diagnosis of CIN across to the cervical lesions. Results There was correlation between the incidence of both P16 and Ki-67 and the diagnosis of the cervical lesions of the patients: P16 positive rate were 0, 71.43%, 100%, 100%, 100% and Ki-67 positive rate were 0, 49.05%, 100%, 100%, 100% set in different pathological changes, the difference was statistically significant (x^2=156.012, 152.727, P<0.001). Comparing P16 and Ki67 semi-quantitative score to diagnose CIN pathology classification to conventional HE pathological grading diagnosis research: the accordance rate of patients with chronic cervical inflammation was 100%, and the one of patients with CIN was 95.45%. The total incidence of HPV infection rate was 67.50%, and as the P16 expression intensity increasees, HPV infection rate increased accordingly:-(57.26%),+(78.57%),++(81.48%),+++(88.00%),++++(90.00%), and the difference of HPV-16, HPV-58, HPV-52, HPV-31, HPV-66 and high-risk hybrid in P16 positive and negative comparison was statistically significant (x^2=4.295, 5.327, 8.807, 13.831, 17.273, 11.489, P<0.05). Conclusion Combined with the P16 and Ki-67 immunohistochemical semi-quantitative score can improve the accuracy and repeatability of the pathological diagnosis of CIN, and the semi-quantitative score of P16 and Ki-67 immunohistochemical staining can reflect the degree of CIN lesions objectively, and The detection of P16 show a certain significance in the prognosis and outcome of cervical CIN lesions with HPV infection. Besides, HPV-16 and HPV-58 should be focused on in treating HPV infection.