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Objective To observe the level of imprinting gene p57kip2 and p27kip1 expression in different hydatidiform moles.To investigate the value of combined detection of p57kip2 and p27kip1 in diagnosis and differential diagnosis of hydatidiform moles.Methods We examined the immunohistochemical staining of p57kip2 and p27kip1 in 30 cases of complete hydatidiform moles and 86 cases of partial hydatidiform moles and 30 cases normal placenta,and also analyze the differences and correlation between the two genes of p57kip2 and p27kip1 in two different patterns of hydatidiform moles.Results The rate of expression of p57kip2 and p27kip1 in complete hydatidiform moles was obviously lower than that in partial hydatidiform moles and nor-mal placenta.There were significant differences in the expression of p57kip2 and p27kip1 among complete hy-datidiform moles,partial hydatidiform moles and normal placenta(P<0.05).p57kip2 had positive correlation with p27kip1 in complete hydatidiform moles(r=0.750,P<0.01),meanwhile there was negative correlation between p57kip2 and p27kip1 in partial hydatidiform moles(r= -1.000,P<0.01).Conclusion The differen-tial expression of p57kip2 and p27kip1 in complete hydatidiform moles and partial hydatidiform moles can be of certain value in the differential diagnosis of hydatidiform moles.Meanwhile,the combined methed is useful to the identification and classification of hydatidiform moles.
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Objective:To explore the relationship between the expression of p57KIP2,cyclin D1,and cyclin E receptors in male breast can-cer(MBC)and its clinical significance.Methods:Data of MBC cases diagnosed in The First Affiliated Hospital of Wenzhou Medical Uni-versity between January 2000 and December 2016 were reviewed.Forty cases of infiltrating ductal carcinoma(IDC)and 20 cases of male ductal carcinoma in situ(DCIS)were selected,and 20 cases of gynecomastia(GYM)were selected as controls.The expression of p57KIP2,cyclin D1,and cyclin E mRNA and protein in the tissue samples obtained from IDC,DCIS,and GYM cases were measured by re-verse transcription polymerase chain reaction and immunohistochemistry,respectively.Results:The expression of p57KIP2mRNA in IDC was 0.18±0.07,which was lower than that in DCIS(0.42±0.05)and GYM(0.75±0.04).The rate of p57KIP2positivity in IDC was 25%(10/40),which was lower than that in DCIS 60%(12/20)and GYM 90%(18/20).There were significant differences in the expression of p57KIP2mRNA and protein among the three groups(P<0.05).The expression of cyclin D1 and cyclin E mRNA in IDC was 0.92±0.12 and 0.96±0.08,which was higher than that in DCIS(0.72±0.06,0.64±0.01)and GYM(0.38±0.03,0.21±0.02),respectively.Cyclin D1 and cy-clin E protein positive rates in IDC were 90%(36/40)and 88%(35/40),which were higher than those in DCIS[80%(16/20),85%(17/20)],and GYM[25%(5/20),20%(4/20)].In IDC tissues,the expression of p57KIP2,cyclin D1,and cyclin E proteins was associated with the clinical stage and histological grade(P<0.05),and the expression of p57KIP2protein was correlated with axillary node metastasis(P<0.05).There was a negative correlation between the expression of p57KIP2and cyclin D1 and between p57KIP2and cyclin E.However,the correlation between cyclin D1 and cyclin E expression was positive(P<0.05).Conclusions:p57KIP2,cyclin D1,and cyclin E may play an im-portant role in the development and progression of MBC.Combined clinicopathological detection of p57KIP2,cyclin D1,and cyclin E can aid future research on MBC.
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Purpose To explore the effects of estrogen receptor antagonist on the expression of estrogen receptor subtype (ERα, ERβ), and p57kip2 protein in human endometrioid carcinoma cells named JEC. Methods The JEC cells (moderately differentiated EC cells) cultured in vitro were treated with β-Estradiol (E2) (10～6 mol/L) and two types of estrogen receptor antagonists, tamoxifen (TAM) and fulvestrant (ICI182780) (10-6 mol/L). After 24, 48, 72 h, MTT was used to detect the growth condition of JEC cells, and the light microscopy and electron microscopy were used to observe the growth condition and morphological changes of cells, Western blot was used to detect the expression of ERα, ERβ, PR-A, PR-B and P57kip2 protein in JEC cells. Results MTT results: Compared with the control group, E2 could promote the proliferation of JEC cells significantly (P＜0.05), and ICI182780 could inhibit the proliferation of JEC cells obviously (P＜0.05). Compared with the E2 group, the proliferation ability of JEC cells in E2 + ICI182780 group were lower(P＜0.05). Morphological change: Compared with the control group, the cells density of E2 group increased obviously, and the pathologic mitosis was easy to seen in some cells. The cells density decreased obviously in ICI182780 group. Compared with E2 group, the cells density of E2 + TAM group and E2 + ICI182780 group were decreased, and pathological mitotic figures were difficult to seen. Western blot results: Compared with the control group, the expression of ERβ protein increased, and the expression of p57kip2 protein decreased in E2 group (P＜0.05). The expression of ERβ protein decreased, and the expression of p57kip2 protein increased in ICI182780 group and TAM group, and the difference was statistically significant between ICI182780 group and control group (P＜0.05). Compared with the E2 group, the expression of ERβ protein decreased, and the expression of p57kip2 protein increased in E2 + ICI182780 group and E2 + TAM group, and the difference was statistically significant between E2 + ICI182780 group and E2 group (P＜0.05). ERa protein of JEC cells did not expressed in experimental group or control group. Conclusion ERa protein are not expressed in JEC cells. ICI182780 have a stronger role in antagonizing estrogen, and may induce the expression of p57kip2 protein by down-regulating the expression of ERβ protein in JEC cells, block the cell cycle progression and inhibit the growth of tumor cells. TAM has a weaker estrogen like effect on the growth of JEC cells. It is possible that combined detection of the expression of ERa and p57kip2 protein in EC has an important reference value for individualized selection of endocrine therapy for EC patients.
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BACKGROUND: Although the morphological features characteristic of products of conception specimens including molar pregnancies are well described, substantial histopathological similarities are observed between the different entities, especially in cases of early pregnancies. Furthermore, there are no current solid criteria that could predict cases with progression to persistent gestational trophoblastic disease. In this study, we aimed to determine the most specific histopathological and immunohistochemical features required for accurate diagnosis that can reliably predict the clinical behavior. METHODS: Sixty-five cases of products of conception were reviewed clinically and pathologically, and any progression to persistent gestational trophoblastic disease (GTD), if present, was noted. Pathological assessment of the archival material included re-cut sections of 5 μm in thickness, routine staining with hematoxylin and eosin and immunohistochemical staining of p57Kip2. RESULTS: Certain histopathological criteria were found to be significant in differentiation between complete hydatidiform mole (CHM) and partial hydatidiform mole including villous shape and outline, villous trophoblast hyperplasia, and atypia in extravillous trophoblasts. There were no significant differences in any morphological or immunohistochemical features between cases with or without subsequent development of GTD. CONCLUSIONS: Histopathological diagnosis of molar pregnancy remains problematic especially in early gestation. Their diagnosis should be stated after a constellation of specific histopathological criteria in order not to miss CHM. p57Kip2 immunohistochemistry is of great value in diagnosis of cases that had equivocal morphology by histopathological examination. However, there were no significant features to predict cases that subsequently developed persistent GTD.
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Female , Pregnancy , Diagnosis , Eosine Yellowish-(YS) , Fertilization , Gestational Trophoblastic Disease , Hematoxylin , Hydatidiform Mole , Hyperplasia , Immunohistochemistry , Molar , TrophoblastsABSTRACT
Objective Analysis the expression and significance of P16INK4 ,P57kip2 and Ki67 in hepatocellular carcinoma .Meth-ods 21 normal liver tissue ,48 hepatocellular carcinoma tissues and 48 corresponding adjacent tissue were collected for this study . Immunohistochemical analysis the expression levels of P16INK4 ,P57kip2 and Ki67 .Results P16INK4 and P57kip2 in hepatocellular carci-noma tissue were significantly lower ,the positive rates were 49 .3% and 34 .2% respectively ,Ki67 was significantly higher than the normal liver tissue and corresponding adjacent tissue ,the difference was statistically significant(P<0 .05) ,the results were consist-ent with the Western blot ;different differentiated group p57kip2 ,Ki67 expression and P16INK4 were significant differences(P<0 .05) . Conclusion Low expression of P16INK4 and P57kip2 ,the higher expression of Ki67 play an important role in the development of hepa-tocellular carcinoma .
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Objective To study the expression of P57kip2 and its clinical significance in hilar bile duct adenocarcinoma.Methods The expressions of P57kip2 in hilar bile duct adenocarcinoma tissues (37 cases) and normal bile duct tissues (32 cases) were determined by immunohistochemical SP methods.The relations between the expression levels of P57kip2 with clinicopathologic parameters were analyzed.Results The positive rate of P57kip2 was 43.2％ (16/37) in bile duct adenocarcinoma,while it was 87.5％ (28/32) in normal duct tissues (P ＜0.01).The expression level of P57kip2 in adenocarcinoma showed no significant association with gender,age or CA19-9 level (P ＞0.05),but they were significantly related with lymph node metastasis,invasion and degree of differentiation (P ＜ 0.05).Conclusions P57kip2 is associated with the occurrence and development of hilar bile duct adenocarcinoma.It may play an important role in invasion and metastasis of hilar bile duct adenocarcinoma.The P57 protein can be used as an index to diagnose hilar bile duct adenocarcinoma.
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Purpose To study the effects of p57kip2, Cyclin D1 on the carcinogenesis and progression of endometrial carcinoma. Meth-ods 100 cases of endometrial adenocarcinoma ( EA) , 20 cases of endometrial intraepithelial neoplasia ( EIN) , 20 cases of hyperpla-sia lesion, 20 cases of endometrial proliferative phase were selected. Different endometrial cells ( well-differentiated endometrial cancer cells Ishikawa, moderately differentiated endometrial cancer cells JEC, poorly differentiated endometrial cancer cells KLE and normal endometrial cells ESC) were cultured. Protein expression of p57kip2, Cyclin D1 was measured by immunohistochemical EliVision meth-ods. The expression of p57kip2, Cyclin D1 protein in different endometrial cells was detected by Western blot. Results The highest expression of p57kip2 protein was in EIN, the higher expression was in endometrial proliferative phase, the low expression was in EA and the lowest expression was in hyperplasia lesions, but only the expression of p57kip2 protein in EIN was higher than that in hyperplasia le-sions (P<0.05). The highest expression of Cyclin D1 protein was in EA and the lowest expression of Cyclin D1 protein was in endom-etrial proliferative phase, expression of Cyclin D1 protein increased gradually in hyperplasia lesions and EIN, p57kip2, Cyclin D1 pro-tein expression in the tissue of EA increased along with the histological grade, all present decreasing trend, but only p57kip2 protein ex-pression related to histological grade ( P<0.05 ) . The highest expression of p57 kip2 protein was in KLE and the lowest expression of p57kip2 protein was in ESC, but only the expression of p57kip2 protein in KLE was higher than that in ESC (P<0.05). The expression of Cyclin D1 in JEC, Ishikawa higher than that in ESC (P<0.05). Conclusion p57kip2, Cyclin D1 are involved in the occurrence and development of endometrial carcinoma, Cyclin D1 is an early event in endometrial carcinoma, but there may also be have abnormal p57kip2 protein by synthesized, synergistically. Cyclin D1 promoting endometrial malignant transformation. Combined detection of p57kip2, Cyclin D1 expression in endometrial carcinoma, to predict the prognosis of endometrial carcinoma has a certain clinical signifi-cance.
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Objective To investigate the differential expression of P57kip2 and CDK5 in neural tube defects t(NTD) from the normal ,and provide the clue for the research of the molecular mechanism of the normal neurula formation .Methods A cDNA mi-croarray containing 1 100 known genes was used to compare differences in P57kip2 and CDK5 gene expression between the normal control group and the retinoic acid(RA)-induced NTD group on embryonic(E) day 9 .5 and 10 .5 .Two differentially expressed genes were randomly selected from the two groups for Northern blotting to verify the results of the cDNA microarray .Results Compared the differences of between P57kip2 and CDK5 in normal and E9 .5 d ,E10 .5 d ,E9 .5 d-NTD ,E10 .5 d-NTD ,P57kip2 and CDK5 expression was significantly up-regulated in the before and after the formation of the normal neurulation ,but them showed a downward trend in retinoic acid (RA)-induced NTD(including two phase E9 .5 d and E10 .5 d) .Conclusion P57kip2 and CDK5 in-volved in the physiological process of NTD ,and provide the useful clue for the research of the molecular mechanism of the normal neurula formation .
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Objective To study the expressions of P57~(kip2) mRNA and genetic instability of P57~(kip2) in human hepatocellular carcinoma (HCC).Methods In situ hybridization(ISH) was used to detect the expression of P57~(kip2) mRNA in HCC.MSI and LOH were detected by PCR-polyacrylamide gel electmphoresis-silver staining method.Results There was no expression of P57~(kip2) mRNA found in normal liver tissue.The expression rate of P57~(kip2) mRNA in both pericancerous cirrhosis and hepatocellular carcinoma was 26.7%(8/30).LOH was not identified in 30 cases on three microsatellite loeies;there were 2 microsatellite loeies showing MSI,the total rate of MSI was 16.7%.There was correlation found between the MSI of D11S1760 locies and the expression of P57~(kip2) mRNA(P＜0.05).Conclusion The disorder expression of P57~(kip2) mRNA indicated that P57~(kip2) might be involved in hepatocarcinogenesis and prognosis.MSI may be one of the reasons that explains the disorder expression of P57~(kip2) mRNA in hepatocarcinogenesis and prognosis.
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Objective: To investigate the effects of FGFR1OP and p57/Kip2 proteins on the genesis and progression of gliomas and their clinical significance. Methods: The expression of FGFR1OP and p57/Kip2 in 54 glioma specimens was detected by SP immunohistochemical technique. The relationship between the ex-pression levels of those proteins and various clinical pathologic factors was evaluated. Results: The expres-sion of FGFR1OP and p57/Kip2 was found in 66.7% and 44.4% gliomas, respectively. The OD value of FG-FR1OP was 0.131±0.010 in high grade gliomas, and 0.118±0.010 in low grade ones, with a statistical signifi-cance (t=-5.497, P=0.000), showing that higher expression of FGFR1OP was significantly associated with glo-ma cell differentiation. The OD value of p57/Kip2 was 0.156±0.008 in high grade gliomas, and 0.165±0.006 in low grade ones, with a statistical significance (t=0.296, P=0.014), showing that lower p57/Kip2 expression was correlated with high grade gliomas. FGFR1OP was negatively correlated with p57/Kip2 in gliomas (r=-0.732, P<0.01). Conclusion: Increased expression of FGFR1OP and/or decreased expression of p57/Kip2 may play an important role in the genesis and progression of gliomas and may indicate a poor prognosis.
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OBJECTIVES: The purpose of this study is to investigate the expression of CDK (Cyclin dependent kinase) inhibitor, p57(kip2) in human ovarian corpus luteum, benign and malignant ovarian tumors. METHODS: 46 women undergoing laparoscopic surgery or laparotomy for ovarian tumors were enrolled. Total 46 formalin-fixed, paraffin-embedded sections of corpus luteum, benign and malignant ovarian tumors were stained by immunohistochemistry for expression of p57(kip2). RESULTS: p57(kip2) was stained in theca cell of growing follicle but not induced in human corpus luteum. There was the expression of p57(kip2) in mature teratoma, immature teratoma and endometrioma but not in epithelial ovarian tumors. CONCLUSIONS: These results showed that p57(kip2) expression may be not important in luteinization of the ovary and seemed not to play a role in development of epithelial ovarian tumors. However, it may involve pathogenesis of mature teratoma, immature teratoma and endometrioma.
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Female , Humans , Corpus Luteum , Endometriosis , Immunohistochemistry , Laparoscopy , Laparotomy , Lutein , Luteinization , Ovary , Teratoma , Theca CellsABSTRACT
Objective To analyze the effect of X-irradiation on the proteins expression of p57kip2 and TGF-β1 in lung cancer cell stain A549 and its clinical significance.Methods Lung cancer cell stain A549 was cultivated and cell,protein was extracted at 6,12,24,36 and 48 hours after X-irradiation by differenl doses(2,4, 8 and 12 Gy).The expression of p57kip2 and TGF-β1 proteins were examined by Western blot.Results The expression of p57kip2 in lung cancer cell stain A549 was very low before X-irradiation.and increased significantly after irradiation with difierent doses and reached the peak level at 12 hours after irradiation(P<0.05).TGF-β1 reached its peak 1evel at 6 hours after irradiation(P<0.05).Conclusions X-irradiation can up-regulate the expression of p57kip2 and TGF-β1 proteins which increased with certain doses.p57kip2 and TGF-β1 could be usedto predict the damage degree of cancer cells by X-ray.
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Objective To study the signification of p57kip2 immunostaining to distinguish molar gestations from hydropic abortions.Methods To observe the p57kip2 immunohistochemical expression in 58 cases of histological hydropic villi which were divided into complete mole(18 cases) ,partial mole(19 cases),hydropic abortion(11 cases)and undetermined hydropic abortion or molar gestations(10 cases) and in 3 normal placentas.Results Normal villi,partial mole and hydropic abortions show positive staining for p57kip2, which expressed in the nuclei of cytotrophoblast and villous mesenchyme,and complete moles show complete absence of staining in the cytotrophoblast and villous mesenchyme.According to the comparison of the diagnosis based on morphology and the one based on p57kip2 stai-ning,the later whose sensitivity is 96% (46/48) confirmed the earlier diagnosis in 58 cases studied and the later conformed to the earlier very well.Conclusion The immunohistochemical staining for p57kip2 is a valuable diagnostic mean to distinguish molar gestations from hydropic abortions and is a sensitive and specific marker for the diagnosis of complete mole.
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OBJECTIVE: This study was to investigate the localization of CDK inhibitor, p57(kip2) in mouse endometrium during the estrus cycle and pre- and peri-implantation periods. METHODS: The p57(kip2) protein was immunostained from endometrium of mouse sacrificed at diestrus, proestrus, estrus, and metestrus cycle, and at day 1-6 post-coitum (p.c.). RESULTS: The staining in the luminal epithelium was very weak in comparison with glandular and stromal cells. In diestrus stage, immunoreactivity of p57(kip2) was heterogeneously strong in parts of decidualized or degenerated stromal cells. In proestrus stage, strong immunoreactivity p57(kip2) was largely found in stromal cells. But, p57(kip2) was showed low immunoreactivity in estrus stage. In metestrus stage, immunoreactivity of p57(kip2) was heterogeneously strong in decidualized stromal cells. In day 1-2 p.c., immunoreactivity of p57(kip2) was low in some endometrial stromal cells. In day 3-4 p.c., immunoreactivity of p57(kip2) was strong in some endometrial stromal cells. In day 5-6 p.c., immunoreactivity of p57(kip2) was strong in decidual cells. CONCLUSION: These suggest that p57(kip2) may play an essential role in endometrial differentiation for maintenance of implantation, especially decidualization of endometrial stromal cells.
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Animals , Female , Mice , Diestrus , Endometrium , Epithelium , Estrus , Metestrus , Phenobarbital , Proestrus , Stromal CellsABSTRACT
PURPOSE: The isoflavones in soy are likely to contribute to the historically low incidence of breast cancer among Asian women who consume traditional diets. The possible role of isoflavones in controlling the expression of p27(kip1) and p57(kip2) has not been previously explored. In this study, the ability of the isoflavone, genistein, to regulate the expression of p27(kip1) and p57(kip2) in breast cancer cells was evaluated. METHODS: The effects of genistein was examined on the expression of p27(kip1) and p57(kip2) at the mRNA level, using the MDA-MB 231 human breast cancer cell lines. RESULTS: By genistein treatment, p27(kip1) mRNA increased significantly in comparison to the control group. In particular, p27(kip1) mRNA level in 10 micrometer and 50 micrometer genistein treated- groups increased about two-folds more than the control. p57(kip2) mRNA was not different from control group. p57(kip2) mRNA decreased slightly only in the 50 micrometer genistein treated-group. PPAR-gamma mRNA level increased slightly according to the concentration-dependent manner of genistein, but it was not significantly different. Conclusions: These results suggest that the up-regulated p27(kip1) by genistein might contribute to cancer prevention or inhibition.
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Female , Humans , Asian People , Breast Neoplasms , Breast , Cell Line , Diet , Genistein , Incidence , Isoflavones , RNA, MessengerABSTRACT
OBJECTIVE: This study was to investigate the expression of CDK inhibitors, p27(kip1) and p57(kip2) in mouse endometrium during the estrus cycle and pregnant period. METHODS: Total RNA and protein were extracted from endometrium of mouse sacrificed at diestrus, proestrus, estrus, and metestrus cycle, and at day 1-6 post-coitum (p.c.), then semi-quantitative RT-PCR and western blotting of p27(kip1) and p57(kip2) was carried out. RESULTS: p27(kip1) and p57(kip2) mRNA was highly expressed in diestrus and proestrus stage than estrus and metestrus stage. In comparison with estrus cycle, p27(kip1) and p57(kip2) mRNA level was highly maintained in gestational endometrium (except p27(kip1) of day 5 p.c). p57(kip2) protein level was relatively low from day 1 p.c. to day 4 p.c. But it was significantly increased in day 5 p.c. and day 6 p.c. CONCLUSION: These results show that p27(kip1) and p57(kip2) may play a role in endometrial differentiation for regular estrus cycle and implantation, and especially p57(kip2) may play an essential role in endometrial differentiation for maintenance of implantation.
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Animals , Female , Mice , Blotting, Western , Diestrus , Endometrium , Estrus , Metestrus , Proestrus , RNA , RNA, MessengerABSTRACT
OBJECTIVE: This study was to investigate the expression of CDK inhibitors, p27kip1 and p57kip2 during the growth and differentiation of mouse placenta. METHODS: Total RNA and protein were extracted from placenta of mouse sacrificed at day 12, 14, 16, 18 post-coitum (p.c.), then semi-quantitative RT-PCR and western blotting of p27kip1 and p57kip2 was carried out, respectively. RESULTS: p27kip1 mRNA was highly expressed in 18 days p.c. then other groups. But, p57kip2 mRNA expression was high in 12, 14, and 16 days p.c., then decreased in 18 days p.c. p27kip1 expression pattern was similar with mRNA. But, p57kip2 was higher in 14 days p.c. than other groups. CONCLUSION: This result shows that p27kip1 may play a role in late period of mouse placental development, and p57kip2 may play a role in middle period of mouse placental development.
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Animals , Mice , Pregnancy , Blotting, Western , Placenta , Placentation , RNA , RNA, MessengerABSTRACT
Objective To investigate the expression of p57kip2 and cyclin D1 in human brain glioma and its clinical significance.Methods The expression of p57kip2 and cyclin D1 was detected by SP immunohistochemical technique in brain glioma(n=55) and normal brain tissues(n=10).Results Positive rate of p57kip2 protein in the 55 cases of brain glioma was 38.2%(21/55),significantly lower than that in normal brain tissues(80%,P
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Aim To explore the effect of 4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on proliferation,differentiation activity in K562 cell line,and to research the mechanisms.Methods Cell proliferation was assessed by MTT assay.Cell differentiation index was analyzed by NBT reduction test.Morphologic changes were observed by Wright's staining in the light microscope. Cell cycle was determined by FCM.The mRNA expression of Cyclin D1,Cyclin E,CDK2,CDK4,CDK6,P21cip1,P27kip1,P57kip2,PCNA mRNA were detected by RT-PCR.While the protein expression of cyclin D1 and CDK4 was detected by Western blot.Results The growth of K562 cells was inhibited in a dose-dependent manner.NBT reduction test indicated that the ATPR could induce differentiation of K562 cells and increase the positive cell ratio.Morphologic changes were observed after Wright's staining using inverted phase contrast microscope.The proportion of cells in G0/G1 phase increased while S phase cells decreased.Cell cycle progression was blocked in the G1 phase.The expression of Cyclin E,cyclin D1,CDK2,CDK4,CDK6 mRNA decreased,while PCNA,P21 cip1,P27 kip1 change was not obvious,but P57 (kip2) mRNA expression was increased.Cyclin D1 and CDK4 protein expressions were reduced as well.Conclusions ATPR inhibits the growth of K562 cells and induces differentiation.P57 kip2 plays a key role in differentiation.Moreover,high level of P57kip2 is regulated via inhibiting its degradation through reducing proteasome-dependent proteolysis,and ATPR plays a role in cell cycle arrest.
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Objective:To assess the relation and clinical significance between p57 kip2 protein and the biological behavior of bladder transitional cell carcinoma(BTCC).Methods:The expression of p57 kip2 protein and PCNA was detected in 50 cases of BTCC,14 normal bladder mucosa by immunohistochemical method.Results:Positive rate of p57kip2 protein in BTCC was 46%,which was significant lower than 78.6% in normal bladder muscosa.( ? 2=4.660, P 0.05);positive rate of PCNA in BTCC was 60 %(30/50),which was significantly higher than 0%(0/14) in normal bladder mucosa( ? 2=15.812, P