Expressions And Significances Of P57～(kip2), P27～(kip1) In Gliomas And Their Relationship With The Pathological Grade

ObjectGlioma is one of the common tumor in nervous system. Its tumorigenesis andprogression are a complex process involved of multigene and multiprocedure. How tocontrol the growth of glioma cells and inhibit the development, recurrence andmetastasis of glioma remain to be elucidated. The abnormality of mammalian cellcycle regulation is closely associated with genesis and progression of tumors, whichhas been a focus of oncological research at present. The normal progress of cellcycle depends on the balance of positive and negative regulation. Cell growth regulat-ing factor include three types factors : cyclins, cyclin-dependent kinases andcyclin-dependent kinases inhibitors (CKIs). Surrounding the CDK, cyclins havepositive effects, and promote the cell proliferation, while CKIs (cyclin-dependentkinases inhibitors, CKIS) have negative contribution. The progress of cell cycle fromG1 to M have many checkpoints, while G1 to S stage is the most importantcheckpoint, because it's a rate limiting stage, and this stage decide the length of cellcycle. If cell pass through this checkpoint, it needn't depend on the motivation ofexogenous division growth signals, and the cell will finish cell cycle.p57^kip2 is an important member of CKIS, and it belongs to the family of Cip / Kip.p57^kip2 can mediate the proceeding of cell cycle mainly by inhibiting the function ofCDK compound. It mainly inhibits these compounds like cyclinE-CDK2,cyclinA-CDK2 and cyclinD-CDK2, which are compounds of G1 and S stage kinases.Therefore the cell can't pass the G1 stage, p27^kip1,a member of the cip/kip family ofthe CDK inhibitors, is also identified as a negative growth regulator present in cells.p27^kip1 binds to a wide variety of cyclin/CDK complexes, inhibits kinase activity, and plays a role in cell-cycle arrest at the G1 phase. In this study, we detected theexpression of p57^kip2 protein and p27^kip1 protein by immunohistochemistry method in50 glioma specimens during operation to investigate their roles in the carcinogenesisand progression of glioma, the relationship between these two genes, as well as theclinicopathological significance of these two genes.Methods50 sample of glioma that were taken in operations in the first clinical college ofChina Medical University from January 2002 to July 2005 were acted as theexperimental group. The age of glioma paitients was from 19 to 74, with a mean age46.14.The experimental group was divided into four groups:12 gliomas of GradeⅠ,15 gliomas of GradeⅡ,13 gliomas of GradeⅢand 10 gliomas of GradeⅣ.Tennormal brain tissues served as control group and the age was from 42 to 57,with amean age 51.3.Using SP immunohistochemistry method, the expressions ofp57^kip2,p27^kip1 in gliomas and nomal brain tissues were detected.ResultsThe positive expression rate of p57^kip2 in glioma of GradcⅠ-Ⅳwere58.33%(7/12),40%(6/15),23.08%(3/13),10%(1/10), respectively. They were all lowerthan nomal brain tissue 70%(7/10).It could be observcd significant difference inexpression of p57^kip2 (in GradeⅣwas lowest and in GradeⅠwas highest). Amongfour groups of glioma, significant difference was identified between the fourgroups(P＜0.05).The positive expression rate of p27^kip1 in glioma were 58.33% (7/12), 46.57%(7/15), 30.77%(4/13),10%(1/10),respectively. They were all lower than nomal braintissue 80%(8/10).It could be observed significant difference in expression of p27^kip1(in GradeⅣwas lowest and in GradeⅠwas highest). Among four groups of glioma,significant difference was identified between the four groups(P＜0.05).Expressions of p57^kip2, p27^kip1 in gliomas correlated with Pathological Grade, ConclusionThe expression of p57^kip2,p27^kip1 is high in low malignant gliomas (WHO gradeⅠ-Ⅱ), and low in high malignant gliomas(WHO gradeⅢ-Ⅳ).The significances ofp57^kip2,p27^kip1 is important in the growth and development of glioma cells, and theirexpression is correlated with the pathological glioma grade. Combined detection ofP57^kip2,p27^kip1 protein is helpful to judge the pathological grade of glioma cells.