Ki-67、P27在肾上腺皮质肿瘤中的表达及意义
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摘要
目的:研究Ki-67与P27在良恶性肾上腺皮质肿瘤中的表达情况,探讨它们作为鉴别良恶性肾上腺皮质肿瘤的生物学参考指标的可行性。
     方法:采用免疫组化法(SP),检测12例正常肾上腺,10例肾上腺皮质腺癌,60例肾上腺皮质腺瘤中Ki-67与P27的表达,并分析它们的表达情况与良恶性肾上腺皮质肿瘤之间的关系。
     结果:
     1.ki-67在正常肾上腺皮质、肾上腺皮质腺瘤、肾上腺皮质腺癌中的表达:(1)正常组与腺瘤组比较无显著差异(P=0.761>0.05)。(2)正常组与腺癌组比较有显著差异(P=0.003<0.05)。(3)腺瘤组与腺癌组比较有显著差异(P=0.001<0.05),且阳性表达率腺癌组(80%)高于腺瘤组(13.33%)。
     2.P27在正常肾上腺皮质、肾上腺皮质腺瘤、肾上腺皮质腺癌中的表达:(1)正常组与腺瘤组比较无显著差异(P=0.512>0.05)。(2)正常组与腺癌组比较有显著差异(P=0.006<0.05)。(3)腺瘤组与腺癌组比较有显著差异(P=0.001<0.05),且阳性表达率腺瘤组(91.97%)高于腺癌组(40%)。
     3.对ki-67LI与P27LI进行等级相关分析,结果显示,r=-0.63,P<0.05,有统计学意义,提示ki-67LI与P27LI呈负相关,即在各组的表达中,Ki-67LI越高P27LI越低。
     4.Ki-67LI在肾上腺皮质腺瘤组与腺癌组中,有显著差异(P<0.01),且腺癌组(11.47%)高于腺瘤组(2.64%)
     P27LI在肾上腺皮质腺瘤组与腺癌组中,有显著两者差异(P<0.01),且腺瘤组(20.36%)高于腺癌组(10.11%)
     提示Ki-67LI与P27LI在腺瘤组和腺癌组中的差异均有统计学意义。
     结论:
     检测Ki-67和P27可能为鉴别良恶性肾上腺皮质肿瘤提供辅助生物学参考指标。联合检测Ki-67和P27可能提高鉴别良恶性肾上腺皮质肿瘤的敏感性,可以考虑将Ki-67LI>4%,P27LI<13%作为肾上腺皮质肿瘤恶性倾向大的辅助参考标准。
Objective:To study the expression of Ki-67,P27 in adrenocortical tumors,and its relationship with adrenocortical carcinoma and adrenocortical adenoma.
     Methods:The methods of S-P Immunohistochemistry was used to detect the expression of Ki-67.P27 in adrenocortical carcinoma(10cases),adrenocortical adenoma(60cases)and normal adrenocortical tissue(12cases).and the expression of Ki-67.P27 was analyzed with relation to adrenocortical carcinoma and adrenocortical adenoma.
     Results:1.There is significant difference in the expression of Ki-67 between adrenocortical carcinoma and adrenocortical adenoma,and the positive rate of adrenocortical carcinoma is significant higher than that in adrenocortical adenoma.2.There is significant difference in the expression of P27 between adrenocortical carcinoma and adrenocortical adenoma,and the positive rate of adrenocortical carcinoma is significant lower than that in adrenocortical adenoma.3.There is the highest expression of Ki-67 and the lowest expression of P27 in adrenocortical tumors.There exist negative correlation between the expression of Ki-67 and P27(P<0.05).There is significant difference in the LI of Ki-67 and that of P27 between adrenocortical carcinoma and adrenocortical adenoma(P<0.01).The cutpoint of LI of Ki-67 was 4%and the cutpoint of P27 was 13%in adrenocortical carcinoma.
     Conclussions:It is suggested that combine detecting the expression of Ki-67 and P27 may be taken as one of biomarkers for differentiation of adrenocortical adenomas from adrenocortical carcinomas.The LI of Ki-67 above 4%and LI of P27 below 13%,is a sensitive indicator of adrenocortical carcinoma.
引文
[1]刘艳平,韩凤霞.医学细胞生物学.中南大学出版社,ISBN 7-81061-435-5/R.006 2001年8月第一版.
    [2]Brown DC,Gatter KC.Ki-67 Protein:the immaculate deception?Histopathology,2002,40:2-11.
    [3]朱晓峰,吕会增,Skp2在人类恶性肿瘤中的研究进展[J].国外医学肿瘤学分册,2004,131,No.3.7-99.
    [4]Shi SR,Tandon AK,Haussmann RR,et al.Immunohistochemical study of intermediate filament proteins on routinely processed,celloidin-embedded human temporal bone sections by using a new technique for antigen retrieval [M],Acta Otolaryngol,1991.
    [5]Polyak K,Kato JY,Solomon MJ,et al.p27Kipl,a cyclin-Cdk inhibitor,links Transforming growthf actor-beta and contactin hibition to cell cycle arrest.Genes Dev,19 94,8(1):9-22.
    [6]Pietenpol JA,Boblander SK,Sato Y,et al.A ssignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.Cancer Res,19 95,55(6):1206-10.
    [7]吴阶平,顾方六.吴阶平泌尿外科学.ISBN 7-5331-3408-7,2004年5月第一版.
    [8]Scholzen T,Gerdes J.The Ki-67 protein:Fromthe known and unknoun.J cell Physiol,2000,182(3):311-22.
    [9]Kuo MY,Hsu HY,Kok SH,et al.Prognoslic role of p27K IP expression in oral squamous cell carcinoma in Taiwan[J],Oroal Oncol,2002,38(2):172.
    [10]Gerdes J.The Ki-67 protein:Fromthe known and unknoun.J cell Physiol,2000,182(3):311-22.
    [11]Duchrow M,Schluter C,Wohlenberg C,et al.Molecular Characterization of the gene locus of the human cell proliferation-associated nuclear pro-tein defined by monoclonal antibody Ki-67.Cell Prolif,1996,29(1):1-12.
    [12]Schmidt MH,Broil R,Bruch HP,et al.The proliferation marker P ki-67becomesmasked to MIB-1 Staining after expression of its tandem repeats.Histochem cell Biol,2002,118(5):415-2
    [13]Asakura T,Takano Y,Iki M,et al.Prognostic value of Ki-67 for recur-rence and progression of superficial Bladder cancer,Jurol,1997,158:385-388
    [14]Wu TT,Chen JH,Lee YH,et al.The Role of bcl-2,P53 and Ki-67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma.Jurol,2000,163:758-760.
    [15]Kirkali Z,Yorukoglu K,Ozkara E,et al.Proliferative activity,angiogenesis and nuclear morphometry in renal cell carcinoma.Int Jurol,2001,8(12):697-703.
    [16]Bantis A,Giannopoulos A,Gonidi M,et al.Expression of P120,Ki-67and PCNAas proliferation biomarkers in imprint smearsof prostate carci-noma and their prognostic smears of prostate carcinoma and their prog-nostic value.Cytopathology,2004,15(1):25-31.
    [17]K Iino,H Sasano,N Yabuki,Y Oki,A Kikuchi,T Yoshimi and H Nagura.DNA topoisomerase Ⅱ alpha and Ki-67 in human adrenocortical neoplasms:a possible marker of differentiation between adenomas and carcinomas[J].Pathol,Sep 1997;10(9):901-7.
    [18]M Terzolo,A Boccuzzi,S Bovio,S Cappia,P De Giuli,A Ali,P Paccotti,F Porpiglia,D Fontana,and A Angeli.Immunohistochemical assessment of Ki-67in the differential diagnosis of adrenocortical tumors[J].ology,Jan 2001;57(1):176-82.
    [19]卢德成,罗佐杰.肾上腺皮质肿瘤Ki67表达和P16蛋白表达的相关性及意义.中国现代医学杂志,15卷20期.文章编号1005-8982 2005.20-3073-03.
    [20]Wachenfeld C,Beuschlein F,Zwermann O,et al.Discerning malignancy in adrenocortical tumors:are molecular markers useful?Eur J Endocrinol,2001,145(3):335-341.
    [21]Marija Drobnjak,Jonathan Melamed,Samir Taneja,et al.Altered expression of p27 and SKP2 proteins in prostate cancer of African American patients[J].Clin Cancer Res,2003,9(7):2613-2619.
    [22]秦维香,张晓艳.增殖细胞核抗原和P27在前列腺癌中的表达及临床意义.中国医院用药评价分析,2007年第7卷第1期.
    [23]H Nakazumi,H Sasano,K Iino,Y Ohashi and S Orikasa.Expression of cell cycle inhibitor p27 and Ki-67 in human adrenocortical neoplasms[J].Mod Pathol,Dec 1998,11(12):1165-70.
    [24]N akayamaK,Ish idaN,Sh iraneM,et al.M icela ckingp27 displayin creasedbod y s iz e,m ultipleo rganh yperplasia,re tinald ysplasia,an dp ituitary tumors.Cell.1996;85(5):707-720
    [1] Hall M, Bates S, Peters G. Evidence for different modes of action of cyclin-dependent kinases inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins. Oncogene, 1995, 11(8): 1581-1588.
    [2] Parry D, Bates S, Mann DJ, et al. Lack of cyclin D-cdk complexes in Rb negative cells correlates with high levels of pl6 tumor suppressou gene product. EM BOJ, 1995, 14(4)-503-511.
    [3] Polyak K, Kato J, Solomon M, et al .p2 7',a cyclin-CDK inhibitor links transforming growth factor-β and conctact inhibitor to cell cyclin arrest.G enes, 1994 8:9- 22.
    [4] Polyak K, Lee MH, Erdjument-BromageH, et al. Cloning of p27'a cyclin-denpent kinase inhibitor and a potential mediator of extracellular an timitogenic signals.Cell, 1994, 78 :59-66.
    [5] Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-CDK Protein kinase activity is related to p21.Cell, 1994,78 (1):67 -74.
    [6] Ponce-Castaneda MV, Lee MH, Latres E,et al.p27: chromosomal Tomapping 12p12-12p13.1 and absence of mutationsin human tumors. Cancer Res, 1995, 55:1211-1214.
    [7] Nomura H, Sawada Y, Fujinaga K, et al. Assignment of the humanp 27 gene to 12p13 and its analysis in leukemia. Gene, 1997, 191:211-218.
    [8] Fero ML, Rivkin M, Tasch M, et al. A syndrome of mulitiorgan Hyperplasia with features of gigantism,tumorihenesis,and female sterility in p27-deficient mice. Cell, 1996, 85 :733-744.
    [9] Cheng J, Willingham T, Shuford M, et al. Cyclins, cyclin-dependent kinases and CDK inhibitors: implications in cell cyclec ontrol and cancer. J ClinIn vest. 1996,97:1983-1988.
    [10] Rivatd N, Lallemain G, Brtel J. et al. Inhibitora of mammalian GI cyclin-depentdent kinase. J Biol Chem, 1996, 27 :18337-18341.
    [11] Russo A A.et al .N ature, 1996, 382: 325-331.
    [12] Reynisdotir I, Polyak K, Iavarone A, et al. Cell cycle control in mamm alian cells:role of cyclin-dependent kinase inhibitors.Genes,1995 Dev, 6 :1197-1213.
    [13] SherrG .Science. 1996, 274(5293): 1672-1677.
    [14] ChengJ, et al. Controling cell proliferation in difeerntiatingt issues: genetic analysis of negativeergulators of G1-S-phasep rogression.Nucleic Acids Res,1996,24:1727-1803.
    [15]Masahir OA,Toshio K,Motosugu K,et al.Possible role of Helicobacter pylori infection in early gastric cancer.Cancer,1994,11:2691.
    [16]Xuan YH,Choi YL,Shin YK,et al.An immunohisto-chemical study of the expression of cell-cycle-regulatedproteins p53,cyclin D1,RB,p27,Ki67 and MSH2 in gallbladder carcinoma and its precursor lesions[J].Histol Histopathol,2005,20(1):59-66.
    [17]李铸,周宁新,吕雅莉.p27蛋白在肝门部胆管癌的表达及临床意义[J].中华现代外科学杂志,2006,3(8):666-669.
    [18]Jarnagin WR,Klimstra DS,Hezel M,et al.Differential cell cycle-regulatory protein expression in biliary tract adenocarcinoma:correlation with anatomic site,pathologic variables,and clinical outcome[J].J Clin Oncol,2006,24(7):1152-1160.
    [19]Traub F,Mengel M,Luick HJ,et al.Prognostic impact of Skp2 and p27 in human breast cancer[J].Breast Cancer Res Treat,2006,99(2):185-191.
    [20]Esposito V,Baldi A,De Luca A,et al.Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer[J].Cancer Res,1997,57(16):3381-3385.
    [21]武跃明.Skp2、p27在急性白血病细胞中的表达及意义[J].2006,46(26):63.
    [22]马振滨,郭光红,高志星.细胞周期抑制剂P27与胃癌[J].滨州医学院学报,2005,28(3):196-198.
    [23]Zheng JY,Wang WZ,Li KZ,et al.Effect of p27(KIP1)on cell cycle and apoptosis in gastric cancer cells[J].World J Gastroenterol,2005,11(45):7072-7077.
    [24]刘晓波,李里,张丹,等.p27蛋白在胰腺癌组织中表达的意义[J].沈阳部队医药,2001,14(3):211-212.
    [25]Culhaci N,Sagol O,Karademir S,et al.Expression of transforming growth factor-beta-1 and p27Kipl in pancreatic adenocarcinomas:relation with cell-cycle-associ-ated proteins and clinicopathologic characteristics[J].BMC Cancer,2005,5:98.
    [26]Kossatz U,Dietrich N,Zender L,et al.Skp2-dependent degradation of p27kip1is essential for cell cycle progres-sion[J].Genes Dev,2004,18(21):2602-2607.
    [27]Li GQ,Zhang HF.Mad2 and p27 expression profiles in colorectal cancer and its clinical significance[J].World J Gastroenterol,2004,10(21):3218-3220.
    [28]Katayose Y,Kim M,Rakkar AN,et al.Promoting apop-tosis:a novel activity associated with the cyclin-depen-dent kinase inhibitor p27[J].Cancer Res,1997,57(24):5441-5445.
    [29]彭民浩,韦建宝,陈滨,等.P27在肝细胞癌中的表达及其临床意义[J].中华肝胆外科杂志,2004,10(1):48-51.
    [30]景英朝,陆永建.星形细胞瘤中P15与P27基因的表达及相关性研究[J].淮海医药,2007,25(1):12-14.
    [31]Kirla RM,Haapasalo HK,Kalimo H,et al.Low expression of p27 indicates a poor prognosis in patients with high-grade astrocytomas[J].Cancer,2003,97(3):644-648.
    [32]Bali A,O'Brien P,Edwards L,et al.Cyclin D1,p53 and p21Wafl/Cipl expression is predictive of poor clinical outcome in serousepithelial ovarian cancer[J].Clin Cancer Res,2004,10(15):5168-5177.
    [33]Kim K,Shim J,Kim J.Overexpression of p21,cyclin E and decreased expression of p27 in DMBA(7,12-dimethylbenzan thracene),induced rat ovarian carcinogenesis[J].Pathol Int,2003,53(5):291-296.
    [34]Tae Y,Kyouns E,Hoon N,et al.Expression of cyclin E and p27(KIP1)in cervical carcinoma[J].Cancer Lett,2000,153(12):41-50.
    [35]Shiozawa T,ShioharaS,KanaiM,et al.Expression of the cell cycleregulator p27(Kipl)in normal squamous epithehum,cervicalintraepithelial neoplasia,and invasive squamous cell carcinoma of the uterine cervix.Immunohistochemistry an d functional aspects ofp27(Kip1)[J].Cancer,2001,92(12):3005-3011.
    [36]Oshita T,Shigemasa K,Nagai N,et al.p27,cyclin E and CDK2 expresion in normal and cancerous endometrium[J].Int J Oncol,2002,21(4):737-743.
    [37]Kim S,Lee S,Gye M.The expression of Cdk inhibitors p27kipl and p57kip2 in mouse placenta an d human choriocarcinoma JEG-3ceHs[J].Placenta,2005,26(1):73-80.
    [38]Migita T,Oda Y,Naito S,et al.Low expression of p27 is associated with tumor size and poor prognosis in patients with renal cell carcinoma.Cancer,2002,94,973-979.
    [39]Hedberg Y,Davoodi E,Ljungberg B,et al.Cyclin E and p27 protein content in human renal cell carcinoma:clinical outcome and associations with cyclin D.Int J Cancer,2002,102,601-607.
    [40]葛建荣,任国平.肾癌中cyclinD1和p27kip1的表达及其意义.临床与实验病理学杂志,J Cclin Exp Pathol 2006Apr,22(2).
    [41]许丽彦,黄峰岐.P27在肾细胞癌中的表达研究.黑龙江医学,Vol.30,No.7Jul.2006.
    [42]Cord Langner,Reinhardvon Wasielewski.expression of p27 and its ubiquitin ligase subunit SKP2 In upper uri-nary tract transitional cell carcinoma[J].Urology.2004,64(3):611-616.
    [43]Joseph J,Del pizzo.Andrew Borkowski,et al.loss ofcell regulators P27 and cyclinE in transitional cell carcinoma of bladder correlates with tumor grade and padent survival[J].AMJ Pathol,1999,155(1):1129-1136.
    [44]Del Pizzo JJ,Borkowski A,Jacobs SC,et al.Loss of cell cycle regulators p27(kipl)and cyclin E in transitional cell carcinoma of the bladder correlates with tumor wade and patient survival[J].Am J Pathol,1999,155(4):1129-1136.
    [45]Korkolopoulou P,Christodoulou P,Konstantinidou AE,et al.Cell cycleregulators in bladder cancer:a multivariate survival study with emphasison p27kip 1[J].Human Pathology,2000,31(6):751-760.
    [46]Kamai T,Takagi K,Asami H,et al.Decreasing of p27 Kipl and cyclin Eprotein level is associated with progression from superficial into invasion bladder cancer.Br J.cancer,2001,84,1242-1251.
    [47]赵健,余新春,P27和Ki-67在膀胱癌的表达及临床意义.浙江临床医学,2007年12月第9卷第12期.
    [48]张运涛.Ki-67及P27基因产物在膀胱移行细胞癌中的表达及其意义.中国医学工程,Vol.12 No.6 Dec,2004.
    [49]李彬.P27 CyclinD1在膀胱癌中的表达及其意义.实用医学杂志,2006年第22卷第22期.
    [50]Lacoste-Collin L,Gomez-Brouchet A,Escourrou G,et al.Expression of p27 in bladder cancers:immunohistochemical study and prognostic value in a series of 95 cases.Cancer letters,2002,186,115-120.
    [51]Santos LL,Amaro T,Pereira SA,et al.Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder.Eur J Surg Oncol,2003,29,74-80.
    [52]Masuda M,Takano Y,Ild M,et al.cyclin-dependent kinase inhibitor p27expression in transitional cell carcinoma of renal pelvis and ureter.Cancer letters,2000,150,183-189.
    [53]Marija Drobnjak,Jonathan Melamed,Samir Taneja,et al.Altered expression of p27 and SKP2 proteins in prostate cancer of African American patients[J].Clin Cancer Res,2003,9(7):2613-2619.
    [54]秦维香,张晓艳.增殖细胞核抗原和P27在前列腺癌中的表达及临床意义.中国医院用药评价分析,2007年第7卷第1期.
    [55]Tsihlias J,kaprsta LR,DeBoer G,et al.Loss of cyclin-dependent kinase inhibitor P27is a novel prognostic,factor inlocalized human prostate adencarcinoma[J].Cancer Res,1998,58(3):542.
    [56]Cheng L,Lloyd RV,Weaver AL,et al.The cell cycle inhibitors p21WAF1 and p27 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.Clin Cancer Res,2000,6,1896-1899.
    [57]Feedland,de Gregorio F,Sacoolidge JC,et al.Predicting biochemical recurrence after radical prostatectomy for patients with organ-confined diseases using p27 expression.Urology,2003,61,1187-1192.
    [58]Stojadinovic A,Brennan MF.Adrenocortical adenoma and carcinoma:histopathological and molecular compar-ative analysis[J].Mod Pathol,2003,16(8):742-751.
    [59]H Nakazumi,H Sasano,K fino,Y Ohashi and S Orikasa.Expression of cell cycle inhibitor p27 and Ki-67 in human adrenocortical neoplasms[J].Mod Pathol,Dec 1998,11(12):1165-70.
    [60]杨艳丽,欧阳金芝.肾上腺皮质肿瘤中PCNA p27和TOPO Ⅱα的表达与其生物学行为的关系.临床泌尿外科杂志,2006年2月第21卷第2期.
    [61]Kuo MY,Hsu HY,Kok SH,et al.Prognoslic role of p27 expression in oral squamous cell carcinoma in Taiwan[J].Oroal Oncol,2002,38(2):172.
    [62]Tsukamoto S,Sugio K,Sakada-I,el al.Reduced expression of cell-cycle regulator p27 correlates with ashortened survival in nonsmall cell lung cancer[J].Lung Cancer,2001.34(1):83.

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