Expression Of P16,Ki-67,Cytokeratin 7 And CDK4 In Cervical Intraepithelial Neoplasia And Correlation With Clinical Outcome

ObjectiveTo study the expressions of P16,Ki67,CK7 and CDK4 protein in different cervical intraepithelial tissues.We aimed to evaluable the correlation and the value in cervical intraepithelial neoplasia(CIN).MethodsThe expressions of P16,Ki67,CK7 and CDK4 were examined in 183 samples which were recruited from May 2019 to January 2020 in the second affiliated Hospital of Fujian Medical University,including chronic cervicitis tissues(n=35),low-grade squamous intraepithelial lesion(LSIL,n=42)and high-grade squamous intraepithelial lesion(HSIL,n=106)by immunohistochemistry.And all hematoxylin-eosin stained slides were reviewed by 2 independent pathologists.We collected the general data of all samples,such as age,pathological and so on.Using the Max Vision staining detects the expressions of P16,Ki67,CK7 and CDK4,and we evaluable the correlation and the value in cervical intraepithelial neoplasia.Result1.General data:In the experiment,the age of chronic cervicitis tissues group,LSIL group and HSIL group were divided into three age groups,21-30 years,31-40 years and over 40 years,and there were no differences in patient age among the groups(χ~2=4.822,P=0.09).Statistical analysis with the delivery times greater than or equal to three showed it was not significantly different among the three groups(χ~2=4.807,P=0.090).Statistical analysis with the abortion times greater than or equal to two showed it was not significantly different among the three groups(χ~2=2.754,P=0.252).According to education,we divided people into 2 categories who completed high school or not,and statistical analysis showed it was no differences among the three groups(χ~2=1.488,P=0.475).2.HPV infection:The HPV infection samples of normal chronic cervicitis tissues group,LSIL group and HSIL group respectively were20(57.1%),41(90.5%),104(98.1%),and the HPV infection was all significantly different among the three groups(χ~2=43.682,P<0.001).The HPV16 or HPV18 infection samples of the three groups respectively were22.9%,38.1%,53.3%,and it was all significantly different among the three groups(χ~2=10.307,P=0.006).In the three groups,we found that the main HPV types among the three groups is 16,52,58,18,33,39.Statistical analysis with the coinfecting HPV types showed it was significantly different among the three groups(χ~2=9.535,P=0.009).3.The expression of P16 in different cervical tissueIn our study,the expression of P16 was located in cytoplasm or nucleus.The positive expression rate among the expression of P16 in chronic cervicitis tissue,LSIL and HSIL were 11.4%,47.6%and 98.1%respectively.The expression of P16 was significantly different among the three groups(χ~2=106.978,P<0.001).4.The expression of Ki67 in different cervical tissueIn the experiment,Ki67 expression is located in nucleus.In chronic cervicitis tissues,Ki67 positive expression is located in the epithelium of the lower 1/3.The Ki67expression is mostly confined to the epithelium of the lower 1/3 in group LISL.In group HSIL,Ki67 was confined 1/3 lower located in the epithelial layer.Cervical disease group Ki67 protein expression positive cells in cervical squamous epithelium in positional distribution<1/3,1/3-2/3,2/3-3/3,the differences have statistical significance(r=0.806,P<0.001).5.The expression of CK7 in different cervical tissue In this study,the expression of CK7 is located in cytoplasm.CK7 in chronic cervicitis tissues,LSIL and HSIL of the positive expression rate were 20.0%,35.7%and 66.0%respectively.The difference among the three groups was statistically significant(χ~2=26.930,P<0.001).6.The expression of CDK4 in different cervical tissueIn our study,the expression of CDK4 is located in cytoplasm or nucleus.It’s in chronic cervicitis tissues,LSIL and HSIL of the positive expression rate were 0%,9.5%and 52.8%respectively.The expression of CDK4 was all significantly different among the three groups(χ~2=46.711,P<0.001).Conclusion1.It shows that HPV types 16,18,52,58,33,39 and patients with multiple HPV infections are more likely to develop HSIL.2.P16,CK7 and CDK4 three immunohistochemical indicators were expressed on cervical lesions,and the positive expression rate in chronic cervicitis tissues.With the aggravation of SIL lesions,the positive expression rate of Ki67 increased,and it means the stronger the cell proliferation activity.3.Combined with four immunohistochemical indicators,the combined detection of P16,Ki67,CK7 and CDK4 is conducive to the clear diagnosis of cervical squamous epithelial lesions and can be used as a set of good diagnostic indicators.