Expression And Critical Role Of P16,Ki-67 And CK7 In Cervical Squamous Intraepithelial Lesions

Objective:In this study,immunohistochemical SP method was used to detect the expression of molecular biomarker P16 protein(P16),proliferating cell nuclear antigen Ki-67(Ki-67)and cytokeratin 7(Cytokeratin,CK7)in different degrees of cervical precancerous lesions,then to explore the relationship between the indicators and cervical precancerous lesions and study the clinical significance.Methods:A total of 160 patients who were admitted to Lianyungang Hospital affiliated to Nanjing Medical University from January 2014 to March 2017 and were diagnosed by routine HE staining by two chief physicians of the department of pathology were enrolled.Among them,96 patients with cervical intraepithelial neoplasia(CIN)were divided into three groups:CIN? group(25 cases),CIN? group(36 cases)and CIN? group(35 cases).The remaining 64 patients with chronic cervicitis were used as the control group.The expression of P16,Ki-67 and CK7 in the cervical tissues of each group was detected by immunohistochemical SP method.The data were analyzed by SPSS 19.0 software.Results 1.Positive expression rate of P16:15.6%in chronic cervicitis group,60.0%in CIN?,97.2%in CIN?,and 100%in CIN?.The positive expression rate increased with the severity of lesions;The difference between CIN group and cervicitis group was statistically significant(P<0.05).2.Ki-67 was not expressed or weakly expressed in cervicitis tissues,and its expression was limited to the lower third of the epithelium;The expression of Ki-67 in CIN? was located in the lower third of the epithelium,and extended to the lower 1/2 or even the whole layer of the epithelium in the CIN? and CIN? groups,showed a positive correlation between expression intensity and CIN level.The positive expression rates of Ki-67 in chronic cervicitis group,CINI,CINII and CINIII were 32.8%,100%,100%and 100%respectively.the difference between the two groups was statistically significant(P<0.05);3.Positive expression of CK7:The positive expression rates of CK7 in each group were 21.5%,68.0%,80.6%,and 94.3%respectively,the rate showed a gradual upward trend with the increase of CIN level;the difference between CIN groups and control group was statistically significant(P<0.05);4.The consistency of the expression of p16,Ki-67 and CK7 with the classification of CIN in each group were analyzed by Kappa test.The K values were 0.546,0.628,and 0.349(P<0.05)respectively,all showed a consistency;Compared with CIN grade consistency:Ki-67 was the most consistent,p16 was the moderate and CK7 showed merely general.5.The diagnostic value of P16,Ki-67 and CK7 alone and in combination for CIN:the area under the ROC curve of the combined test(0.978)was higher than the area under the curve of testing alone(0.930,0.966,0.837 respectively)(P<0.05),suggesting that the combined detection may have better diagnostic value and higher accuracy.In the separate test,p16 and Ki-67 also showed a good diagnostic performance,but the accuracy was slightly worse compared with the combined test,while the detection of CK7 alone had only certain diagnostic value,and the diagnostic efficacy was only general(P<0.05);The sensitivity of the combined detection was 93.9%and the specificity was 92.4%.In the combination of sensitivity and specificity,the combined detection was superior to the single detection.Conclusion:1.The positive expression of P16,Ki-67 and CK7 is positively correlated with the degree of cervical lesions,and can be used as molecular markers for cervical precancerous lesions;2.Combined detection may improve the diagnostic value of cervical lesions and could be applied to the grading diagnosis of cervical precancerous lesions,which would have a certain predictive value for cervical precancerous lesions.