卵巢癌组织中CREB结合蛋白和P53蛋白的表达及其临床意义
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摘要
目的检测CREB结合蛋白(CBP)和P53蛋白在卵巢癌中的表达,明确CBP突变的位置在氨基端还是羧基端,并分析CBP和P53蛋白的表达与临床病理特征之间的关系以及他们之间的相关程度,探讨他们在卵巢癌的发生、发展中的作用。方法采用免疫组化法检测67例上皮性卵巢癌,18例正常卵巢组织中,CBP(C-20)、CBP(N-22)和P53蛋白表达情况。结果 (1)CBP(N-22)和P53在卵巢癌中(阳性表达分别为48/67,37/67)表达明显高于正常卵巢组织(阳性表达例数分别为0/18,2/18)(P=0.000,P=0.000),CBP(C-20)在卵巢癌中阳性表达数为0,提示CBP的突变位点在CBP(C-20)。(2)CBP和P53的阳性表达与肿瘤的分期及淋巴转移有关,随着分期的增加,两者的表达明显增高,淋巴结转移者阳性表达明显高于无转移者,而与年龄、肿瘤的组织学类型、组织的分化程度无明显的相关性。(3)CBP和P53二者的表达呈正相关(r=0.432,P=0.000)。结论在卵巢癌中,CBP的突变位点在CBP(C-20),与卵巢正常组织相比,在卵巢癌中CBP和P53的表达明显增高,与分期及淋巴转移有关,而与年龄、肿瘤的组织学类型、组织的分化程度无显著的相关性,且两种蛋白的表达呈显著正相关性,提示CBP和P53可能协同参与了卵巢癌的发生、发展过程。
Objective To investigate the expression of CBP(C-20)、CBP(N-22)and P53 protein in human epithelial ovarian malignant tumor,to make clear the position of mutations whether(C-20)or CBP(N-22),and to explore the relationship to clinicopathological characters of human epithelial ovarian malignant tumor,and explore the correlation between CBP and P53 protein expression.To the end,we learn the effect of them in the growth and development of tumor.Methods The expression of CBP(C-20)、CBP(N-22)and P53 protein in 67 paraffin embedded ovarian cancer and 18 normal ovarian tissues were detected by immunohistochemistry.Results(1)The protein expression of CBP(N-22)and P53 was higher in ovarian cancer(The positive expression case 48/67,37/67) than that in normal ovarian tissues(The positive expression case 0/18,2/18)(P=0.000,P=0.000),the positive expression case of CBP(C-20)was 0,this suggest the position of mutations CBP was(C-20).(2)The expression of CBP(N-22)and P53 protein has significant correlation with stage and lymph node metastasis,there was an increased trend of protein expression of CBP(N-22)and P53 accompanying with the increased stage and lymph node metastasis.The expression of CBP(N-22)and P53 protein has no significant correlation with the age,histological type,grade.(3)There was significant positive correlation between CBP and P53 protein expression in human ovarian cancer(r=0.432,P=0.000).Conclusion In human epithelial ovarian malignant tumor,the position of mutations CBP was CBP(C-20),the expression of CBP(N-22)and P53 protein was higher in ovarian cancer compared with in normal ovarian tissues.The expression of CBPand P53 protein has significant correlation with stage and lymph node metastasis,there was no significant correlation with the age,histological type,grade.There was significant positive correlation between CBP and P53 protein expression in human ovarian cancer which prognosticates that CBP and P53 protein could participate in the development and growth of ovarian cancer in cooperation.
Objective To investigate the expression of CBP(C-20)、CBP(N-22)and P53 protein in human epithelial ovarian malignant tumor,to make clear the position of mutations whether(C-20)or CBP(N-22),and to explore the relationship to clinicopathological characters of human epithelial ovarian malignant tumor,and explore the correlation between CBP and P53 protein expression.To the end,we learn the effect of them in the growth and development of tumor.Methods The expression of CBP(C-20)、CBP(N-22)and P53 protein in 67 paraffin embedded ovarian cancer and 18 normal ovarian tissues were detected by immunohistochemistry.Results(1)The protein expression of CBP(N-22)and P53 was higher in ovarian cancer(The positive expression case 48/67,37/67) than that in normal ovarian tissues(The positive expression case 0/18,2/18)(P=0.000,P=0.000),the positive expression case of CBP(C-20)was 0,this suggest the position of mutations CBP was(C-20).(2)The expression of CBP(N-22)and P53 protein has significant correlation with stage and lymph node metastasis,there was an increased trend of protein expression of CBP(N-22)and P53 accompanying with the increased stage and lymph node metastasis.The expression of CBP(N-22)and P53 protein has no significant correlation with the age,histological type,grade.(3)There was significant positive correlation between CBP and P53 protein expression in human ovarian cancer(r=0.432,P=0.000).Conclusion In human epithelial ovarian malignant tumor,the position of mutations CBP was CBP(C-20),the expression of CBP(N-22)and P53 protein was higher in ovarian cancer compared with in normal ovarian tissues.The expression of CBPand P53 protein has significant correlation with stage and lymph node metastasis,there was no significant correlation with the age,histological type,grade.There was significant positive correlation between CBP and P53 protein expression in human ovarian cancer which prognosticates that CBP and P53 protein could participate in the development and growth of ovarian cancer in cooperation.
引文
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[13]Avraam K,Pavlakis K,Papadimitriou C,et al.The prog-nostic and predictive value of ERCC-1,p53,bcl-2and baxin epithelial ovarian cancer[J].Eur J Gynaecol Oncol,2011,32(5):516-520.
[2]Giordano A,Avantaggiati ML.p300and CBP:partners forlife and death[J].J Cell Physiol,1999,181(2):218-230.
[3]Kishimoto M,Kohno T,Okudela K,et al.Mutations anddeletions of the CBP gene in human lung cancer[J].ClinCancer Res,2005,11(2Pt 1):512-519.
[4]Gayther SA,Batley SJ,Linger L,et al.Mutations trunca-ting the EP300acetylase in human cancers[J].Nat Genet,2000,24(3):300-303.
[5]Bykov VJ,Wiman KG.Novel cancer therapy by reactiva-tion of the p53apoptosis pathway[J].Ann Med,2003,35(7):458-465.
[6]Pan X,Zhao J,Zhang WN,et al.Induction of SOX4byDNA damage is critical for p53stabilization and function[J].Proc Natl Acad Sci USA,2009,106(10):3788-3793.
[7]Ishihama K,Yamakawa M,Semba S,et al.Expression ofHDAC1and CBP/p300in human colorectal carcinomas[J].J Clin Pathol,2007,60(11):1205-1210.
[8]Selvakumaran M,Lin HK,Miyashita T,et al.Immediateearly up-regulation of bax expression by p53but not TGFbeta 1:aparadigm for distinct apoptotic pathways[J].On-cogene,1994,9(6):1791-1798.
[9]Bilyk OO,Pande NT,Buchynska LG.Analysis of p53,p16(INK4a),pRb and Cyclin D1expression and human papil-lomavirus in primary ovarian serous carcinomas[J].ExpOncol,2011,33(3):150-156.
[10]Godoy H,Mhawech-Fauceglia P,Beck A,et al.Expres-sion of poly(adenosine diphosphate-ribose)polymeraseand p53in epithelial ovarian cancer and their role inprognosis and disease outcome[J].Int J Gynecol Pathol,2011,30(2):139-144.
[11]González-Rodilla I,Verna V,Muoz AB,et al.Expressionof the apoptosis-related genes Bcl-2and p53in clinicalsamples from endometrial carcinoma patients[J].Anti-cancer Res,2011,31(12):4191-4193.
[12]Skírnisdóttir IA,Sorbe B,Lindborg K,et al.Prognosticimpact of p53,p27,and C-MYC on clinicopathologicalfeatures and outcome in early-stage(FIGOⅠ-Ⅱ)epithe-lial ovarian cancer[J].Int J Gynecol Cancer,2011,21(2):236-244.
[13]Avraam K,Pavlakis K,Papadimitriou C,et al.The prog-nostic and predictive value of ERCC-1,p53,bcl-2and baxin epithelial ovarian cancer[J].Eur J Gynaecol Oncol,2011,32(5):516-520.