The Expression And Clinical Significance Of P16 And Ki67 In Cervical Intraepithelial Neoplasia

Objective:Squamous intraepithelial lesion,SIL,is an abnormal growth of squamous epithelial cells on the surface of the cervix.And it is one of the precancerous lesions of cervical cancer.It is the key step of the progression from normal cells to cancer.Most cases of CIN(Cervical intraepithelial neoplasia)remain stable or are eliminated by the person's immune system without need for intervention.About 90% of CINI retreat within two years,and about 50% of CINII will naturally subside within 2 years,while a small proportion of untreated cases may progress to cervical cancer.Due to the certainty of the morphological and pathological features of CINII between CINI and CINIII,the diagnostic consistency of CINII grades among different pathologists is affected,resulting in the lack of clinical overtreatment or undertreatment.Therefore,in order to improve the repeatability of cervical squamous intraepithelial lesion diagnosis between different pathologists,the present study intends to use immunohistochemistry to detect the expression of P16 and Ki67 in cervical lesions and to reclassify cervical squamous epithelial lesions.In order to improve the accuracy and reproducibility of cervical intraepithelial neoplasia diagnosis..Materials:220 cases were selected from The Affiliated Hospital Of Qingdao University from December 2015 to June 2017 period,age from 23 to 64 years old,with an average of 40.35(±8.4)years old,who are diagnosis in pathological of cervical lesions.There were 20 cases of chronic cervicitis,34 cases of CIN I,65 cases of CIN II,101 cases of CIN III(include 6 cases of carcinoma in situ).They are divided into 4 groups: group inflammation,CIN I group,CIN II group,CIN III group.Method:The paraffin blocks of all patients were loaned from the Department of Pathology in our hospital and stained with immunohistochemistry.Senior pathologists are asked to observe the expression of P16 and Ki67 in each group and perform semi-quantitative grading.P16 is divided into(-),+,++,+++,++++,Ki-67 is divided into +,++,+++,++++.Chi-square test and Fisher's exact test were used to analyze the expression levels of cervical intraepithelial lesions.Then according to the combination of the two factors to re-classify the cervical intraepithelial lesions,the consistency of the results of the two diagnostic criteria was analyzed by the Gamma method and the Kappa index.Results:1.The positive rate of P16 in the CIN group was 87.50%,and the positive rates in the CIN I group,the CINII group,and the CIN III group were 38.24%,93.85%,and 100%.The Fisher exact test for the CIN grade group was 281.314(P<0.001),indicating that P16 expression intensity was significantly different among the CIN groups.The Gamma correlation coefficient of P16 was 0.985(P<0.01).2.The positive rate of Ki67 in the CIN group was 94.50%,and the positive rates in the CIN I group,the CINII group,and the CIN III group were 70.59%,98.46%,and 100%.The value obtained by Fisher's exact test was 379.004(P<0.001).The Gamma correlation coefficient of Ki67 was 0.988(P<0.01).3.Combining the expression of P16 with Ki67,the Kappa index of P16 and Ki67 is 0.465.It can be considered that the expression of P16 and Ki67 in the CIN group is in good agreement and positive correlation.Semi-quantitative combination of P16 and Ki67 reclassified cervical intraepithelial lesions.The diagnostic consistency of chronic cervicitis was 100%.The diagnostic consistency of CIN was 90.50%(181/200).And the Person correlation index was 0.958(P<0.001),the Kappa index was 0.871(P<0.001),and the Wilcoxon rank sum test coefficient was 0.932(P<0.001).It can be considered that the immunohistochemistry combined grading method and the HE staining method Better consistency in the diagnosis of cervical intraepithelial lesions.Conclusion:1.The expression of P16 in cervical intraepithelial lesions was different in each group.And its expression intensity becomes stronger with the increase of cervical intraepithelial lesion grade.2.The expression of Ki67 in cervical intraepithelial lesions varies among groups.And its expression intensity becomes stronger with the increase of cervical intraepithelial lesion grade.3.P16 and Ki67 combined semi-quantitative statutory grade and HE staining method are better for the diagnosis of cervical intraepithelial lesions.4.HE staining combined with immunohistochemistry semi-quantitative method can significantly improve the accuracy and reproducibility of cervical intraepithelial neoplasia,especially CINII,and reduce errors caused by subjective factors.