The Expression And Significance Of Cyclinb1, Cdk1, P27 In Cervical Squamous Cell Carcinoma

The cervical cancer is one of the most familiar gynecology malignant tumors, only next to mammary glands cancer in the global women malignant tumor outbreak rate,be placed in the second.The vast majority of them is squamous cell carcinoma.Although the cervical cancer of the earlier period examine a patient to develop with treatment very quickly,the outbreak rate of the cervical cancer at some nations and the region have augmentative trend in recent years,especially to young turn a development.And,on the clinic,young or later period the another case combine not a few see.Whether the normal cells or the cancer cells,both increase to living through the cell cycle,just the regulation of the cell cycle take place a change in the cancer cells.Therefore it have a necessity to study the outbreak mechanism of the cervical squamous cell carcinoma in the cell cycle further,understand the biology behavior of the cervical squamous cell carcinoma for the clinic,instruction the treatment provide a help.The procedure control of the cell cycle mainly through the common function of various cyclin(the cell cycle protein),CDK(the cyclin-dependent protein kinase) and CDI(the inhibitor of the CDK) to carry out.Cyclin(the cell cycle protein),which is synthesizes continuously a backlog continuously in the cell period and the activity appear the periodic variety,is a set of protein with similar structure,known together as the cyclin family,currently have 8 kinds of members,named cyclinA,B,the C... H.Each kind of type with several isoforms.As regulatory subunit,they need combine different catalytic subunit(cyclin-dependent protein kinase,CDK) to form the compound(cyclin-CDK),thus to modify the function protein phosphorily,and control the cell cycle to carry on.The CyclinB1 is one of the main components to control the cell cycle G₂/M restriction.CDK(cyclin-dependent protein kinase) is a group of serine-threonine(Ser-Thr) protein kinase,is found that seven members having vary degrees of homology,named to CDK1,2,3...7.CDK contain catalytic subunit,but it need be provided regulating cyclin subunit to have activity,so they usually appear in cyclin-CDK complex forms. CDK also bind with the CDI(cyclin dependent kinase inhibitor) to inhibit the cell cycle.CDK1 also called cdc2(cell division cycle gene),the study found that cdc2 encoding protein is CDK1,cyclinB-cdc2 compound is the importance constitute part of M period promote factor(the M phase-promoting factor) or called the maturity promote the factor MPF(the maturation-promoting factor),and it's important to drive cells into the critical M period.Because of the cdc2 s important role,in 1991 a Lengquangang laboratory cell cycle seminar decided to name cdc2 as the first family of CDK,CDK1.CDI is the inhibitor of the CDK,with the non-covalent CDK to inhibit the activity of CDK,which is one of the important confrontation mechanisms involved in cell cycle inspection mechanism.The CDI of Mammalian cells include Ink4(inhibitor of CDK4 acronym),Kip(kinase inhibition protein),Kip including p21,p27 and p57. P27 and cyclin-CDK complexes combined,the latter whether have the inhibition role depends largely on the quantity of p27,the so-called chemical dosage form to function,which is one of its characteristics.Another feature of P27 role is non-specificity,it can inhibit the activity of all CDK.P27 has a higher level in G₀-phase and decrease gradually from the G₀- phase to S-phase.P27 stimulated mainly by induced expression.A study showed that:wild-type p27 gene into tumor cells allows cells in G0/G1 stagnation.This study by immunohistochemistry methods,detected the protein expression of cyclinB1,CDK1 and P27 from 18 cases of normal cervical tissue,19 cases of cervical intraepithelial neoplasia(Ⅱ,Ⅲlevel) tissue,and 56 cases of cervical squamous cell carcinoma in cyclinB1,CDK1,the P27 protein expression,and analysis the relationship between the expression of the three protein in cervical squamous cell carcinoma and clinical pathology,and analysis the relationship of the positive expression in cervical squamous cell carcinoma,and discuss the role of cyclinB1,CDK1,P27 in the development of cervical squamous cell carcinoma and the prognostic value,which provide a experimental basis for the gene therapy of cervical squamous cell carcinoma.Methods1.Immunohistochemical was used to detect the protein expression of cyclinB1, CDK1 and P27 from 18 cases of normal cervical tissue,19 cases of cervical intraepithelial neoplasia(Ⅱ,Ⅲlevel) tissue,and 56 cases of cervical squamous cell carcinoma and the relationship between protein expressions and clinicopathological features were analyzed accordingly.Besides,the relationships between the expression of cyclinB1,CDK1 and P27 were also analyzed.2.Statistical analysis:The SPSS12.0 statistical package program 10.0 was used for all analysis.Association between the variables were tested byχ2 test and FISH exact probability method.The correlation analysis was analyzed by Spearman rank correlation,α=0.05 were deemed to a statistically significant test of the standard.Results1.the positive rates of cyclinB1 in normal cervix tissue,cervical intraepithelial neoplasia(Ⅱ,Ⅲlevel) tissue and cervical squamous cell carcinoma were 11.1%(2/ 18),57.9%(11/19),76.8%(43/56).The positive rate of cyclinB1 in CIN is higher than in normal cervix tissue,and the rate in cervical squamous cell carcinoma is higher than in normal tissue and CIN,the differences are statistically significant(P＜0.05).T2.the positive rates of CDK1 in normal cervix tissue,cervical intraepithelial neoplasia (Ⅱ,Ⅲlevel) tissue and cervical squamous cell carcinoma were 5.6%(1/18),36.8% (7/19),71.4%(40/56).The positive rate of CDK1 in CIN is higher than in normal cervix tissue,and the rate in cervical squamous cell carcinoma is higher than in normal tissue and CIN,the differences are statistically significant(P＜0.05).3.The positive rate of P27 in normal cervix tissue,was the highest rates of 94.4% (17/18),the positive rate of P27 in cervical cancer was the lowest rate of 24.0% (12/56).There were significant differences between the two group(P＜0.05).The positive rate of P27 in CIN was 47.4%(9/19),which is significantly lower than normal cervix tissue,higher than cancer organizations,the differences are all significant(P＜0.05).4.The positive rate of cyclinB1,CDK1,P27 in cervical squamous cell carcinoma was not associated with tumor histological type and clinical stage(P＞0.05),P27 is particularly,but was significantly associated with histological grade(P＜0.05).The positive rate of cyclinB1 in cervical squamous cell carcinoma-Ⅰ,Ⅱ,Ⅲwere 61.5% (6/13),84.0%(21/25),88.9%(16/18),83.3%(15/18).The positive rate of CDK1 in cervical squamouscell carcinoma-Ⅰ,Ⅱ,Ⅲwere 46.2%(5/13),80.0%(20/25),83.3%(15/18).The positive rate of P27 protein expression in cervical squamous cell carcinoma -Ⅰ,ⅡandⅢwere 46.2%(6/13),20.0%(5/25),5.6%(1/18).The positive rate of cyclinB1,CDK1 in cervical squamous cell carcinoma was not associated with lymph node metastasis(P＞0.05).The positive rate of P27 in lymph node metastasis of cervical cancer was 5%(1/20),significantly lower than that of cervical cancer without lymph node metastasis Organization 30.6%(11/36)(P＜0.05).5.The joint expression rate of cyclinB1 and cdk1 in cervical squamous cell carcinoma was 57.1%(32/56),but there was not significant correlation between the expression of them(P＞0.05).There was inversely correlation between positive expression of CyclinB1 and p27(r=-0.331,P＜0.05).There was inversely correlation between positive expression of CDK1 and p27(r=-0.344,P＜0.05).Conclusion1.The positive expression of cyclinB1 and CDK1 is followed by increasing from normal cervical epithelial,CIN to cervical squamous cell carcinoma,suggest that they participate in the process of the development of cervical cancer.2.The expression rate of cyclinB1,CDK1,P27 in cervical squamous cell carcinoma have not relation with tumor histological type,clinical stage,but have notable relations with histological grade.The positive rate of P27 in cervical squarnous cell carcinoma was associated with lymph node metastasis.Because the histological grade is closely related with the prognosis of cervical cancer,the detection of cyclinB1,CDK1,P27 can be used as the evaluation of patients with cervical cancer and the prognosis of survival.4.The relativity analysis of the expressions of cyclinB1,CDK1,P27 show,cyclinB 1,the CDK1 all presents with P27 in the expression of the scale cancer negative related,hint threes to in the temple neck scale the occurrence of the cancer the development the process certainly be in conjunction with a function,three consociation examination of the index signs evaluate after contribute to the evaluation of the temple neck scale cancer biology characteristic and strengthen to prepare.5.The relativity analysis of the expressions of cyclinB1,CDK1,P27 show that:There was inversely correlation between positive expression of CyclinB1,CDK1 and p27 in cervical squamous cell carcinoma,which may play some role in conjunction with a function in the growth and progression of cervical squamous cell carcinoma.There will have contribution to evaluate the biology characteristic and strengthen prognosis in cervical squamous cell carcinoma with consociation examination of them.