The Expression And Significance Of PCNA, CDK4and P16^INK4a In Nonneoplastic Epithelial Disorders Of Vulvar

Objective: The immunohistochemistry method was used toevaluate the expression of proliferation cell nuclear antigen （PCNA）, cyclindependent kinase （CDK）4and cyclin dependent kinase inhibitor （CDKI）protein p16^INK4ain nonneoplastic epithelial disorders of vulva （NNEDV）. Theirsignificance and relationship in the pathogenesis of NNEDV from aspects ofcell proliferation and cell cycle control were explored so as to provide newexperimental basis for prevention and treatment of NNEDV.Methods:52vulvar lesion samples（lesions group） and52vulvar skinsurrounding the lesions samples（the skin of lesion-adjacent group） werecollected from NNEDV patients, lesions group include27samples withsquamous hyperplasia of vulva（VSH）,14samples with lichen sclerosus ofvulva（VLS） and11samples containing both lesions.25normal vulvar skinsamples were collected from patients receiving perineal repair operation ascontrol group. Peroxidase labeled rabbit two step immunochemical staining kitwas used to determine the expression of PCNA,CDK4and p16^INK4ain threegroups and the mean optical density（MOD） of positive cells in each group wasanalyzed with Image Pro6.0and expression status in each group and theircorrelations were analyzed. Statistical methods: All data were processed withSPSS21.0software and the significant level was defined as P<0.05.Results:1.The expression of PCNA in lesions group, the skin of lesion-adjacent group and control group:（1） PCNA expression of the generaltrend in the three groups are as follows: lesions group> the skin oflesion-adjacent group>control group, expression of PCNA in lesions group wassignificantly higher than those in the skin of lesion-adjacent group and controlgroup（P<0.05）;（2） Comparison of PCNA expression among VSH,VLS andmixed lesions group showed no significant differences（P>0.05）;（3） Expressionof PCNA in the skin of lesion-adjacent group and control group showed nosignificant difference（P>0.05）.2. The expression of CDK4in lesions group, theskin of lesion-adjacent group and control group:（1） Expression of CDK4inlesions group and the skin of lesion-adjacent group were significantly higherthan that in control group（P<0.05）;（2） Comparison of CDK4expressionamong VSH,VLS and mixed lesions group showed no significantdifferences（P>0.05）;（3） Expression of CDK4in lesions group and the skin oflesion-adjacent group showed no significant difference（P>0.05）.3. Theexpression of p16^INK4ain lesions group, the skin of lesion-adjacent group andcontrol group:（1） p16^INK4aexpression in lesions group was significantly lowerthan those in the skin of lesion-adjacent group and control group（P<0.05）;（2）Comparison of p16^INK4aexpression among VSH,VLS and mixed lesions groupshowed no significant differences（P>0.05）;（3） p16^INK4aexpression in the skinof lesion-adjacent group and control group showed no significantdifference（P>0.05）.4. The expression of PCNA and CDK4in control group（r=0.341, P=0.095>0.05） showed no correlation, as well as in the skin of lesion-adjacent group（r=0.049, P=0.729>0.05） while positive correlation wasobserved in VSH（r=0.707, P=0.000<0.05）, VLS（r=0.594, P=0.025<0.05） andmixed lesions group（r=0.604, P=0.049<0.05）.5. The expression of PCNA andp16^INK4ain control group（r=0.192, P=0.358>0.05） showed no correlation, aswell as in the skin of lesion-adjacent group（r=0.006, P=0.965>0.05） whilenegative correlation was observed in VSH（r=-0.406, P=0.035<0.05）,VLS（r=-0.757, P=0.002<0.05） and mixed lesions group（r=-0.855,P=0.001<0.05）.6. The expression of and CDK4and p16^INK4ain controlgroup（r=-0.315,P=0.126>0.05） and the skin of lesion-adjacent group（r=-0.042,P=0.769>0.05） showed no correlation, as well as in VSH（r=-0.335,P=0.088>0.05）, VLS（r=-0.207, P=0.477>0.05） and mixed lesionsgroup（r=-0.375, P=0.255>0.05）.Conclusion：1.The NNEDV pathogenesis might be due to active epithelialcell proliferation of vulvar skin, acceleration of cell cycle progression and thefailure of the negative regulation of cell cycle.2. The epithelial cells aroundlesions may have propensity of abnormal proliferation.3. Even cell cycleimbalance existed in the pathogenesis of NNEDV, it may still had distinctdifference with damaged cell cycle system in malignant lesion cells.