磷酸化信号传导和转录激活因子3和端粒酶逆转录酶在脂溢性角化病中的表达及其意义
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摘要
目的研究磷酸化信号传导和转录激活因子3和端粒酶逆转录酶在脂溢性角化病中的表达及其意义。
方法选择鳞状细胞癌、脂溢性角化病、正常皮肤各20例，运用免疫组织化学方法，观察细胞细胞中磷酸化信号传导和转录激活因子(PSTAT3)和端粒酶逆转录酶(hTERT)的表达水平，并进行比较。
结果1、磷酸化信号传导和转录激活因子3(PSTAT3)在20例脂溢性角化病皮损表达中，14例表达呈阴性，6例表达阳性，阳性率30％；20例鳞状细胞癌皮损中，12例表达呈阴性，8例表达呈阳性，阳性率40％；20例正常皮肤组织中均为阴性表达。磷酸化信号传导和转录激活因子3(PSTAT3)在恶性皮肤肿瘤中的阳性表达率明显高于脂溢性角化病(P＜0.05)；而在脂溢性角化病中的阳性表达率明显高于正常皮肤(P＜0.05)。2、端粒酶逆转录酶(hTERT)在20例脂溢性角化病皮损表达中，14例表达呈阴性，6例表达阳性，阳性率30％；20例鳞状细胞癌皮损中，10例表达呈阴性，10例表达呈阳性，阳性率50％；20例正常皮肤组织中，19例表达呈阴性，1例表达呈阳性，阳性率为5％。端粒酶逆转录酶(hTERT)在恶性皮肤肿瘤中的阳性表达率明显高于脂溢性角化病(P＜0.05)；而在脂溢性角化病中的阳性表达率明显高于正常皮肤(P＜0.05)。
结论1、磷酸化信号传导和转录激活因子PSTAT3和端粒酶逆转录酶hTERT与肿瘤的发生发展及增殖程度密切相关；2、脂溢性角化病是一种有潜在恶变倾向的良性肿瘤。
Objective To investigate the expression and significance of Signal transducer andactivator of transcription 3(PSTAT3) phosphorylation and Human TelomeraserReverse Transcriptase (hTERT) in Seborrheic Karatosis.
Methods Immunohistochemistry technique was employed to measure theexpression of PSTAT3 and hTERT in skin tissue from 20 cases of skin squamous cellcarcinoma(SCC), 20 cases of seborrhoeic keratosis(SK) and 20 normal subjects.
Results 1. 6 cases of SK and 8 cases of SCC expressed PSTAT3 protein and therewas no PSTAT3 protain expression on normal skin. Expression of PSTAT3 in SCCwas at a higher level than that of SK, also, the difference of expression of PSTAT3 hasobvious significance between SK and normal skin.2. 6 cases of SK, 10 cases of SCCand 1 case of normal skin expressed hTERT. Expression of hTERT in SCC was at ahigher level than that of SK, also, the difference of expression of PSTAT3 has obvioussignificance between SK and normal skin.
Conclusion 1. The levels of expression of PSTAT3 and hTERT was associatedclosely with the criticial stages in cutaneous tumor in development.2. seborrhoeickeratosis(SK) is a kind of benign skin tumor, but it has potential cutaneouscarcinomas formation.
方法选择鳞状细胞癌、脂溢性角化病、正常皮肤各20例，运用免疫组织化学方法，观察细胞细胞中磷酸化信号传导和转录激活因子(PSTAT3)和端粒酶逆转录酶(hTERT)的表达水平，并进行比较。
结果1、磷酸化信号传导和转录激活因子3(PSTAT3)在20例脂溢性角化病皮损表达中，14例表达呈阴性，6例表达阳性，阳性率30％；20例鳞状细胞癌皮损中，12例表达呈阴性，8例表达呈阳性，阳性率40％；20例正常皮肤组织中均为阴性表达。磷酸化信号传导和转录激活因子3(PSTAT3)在恶性皮肤肿瘤中的阳性表达率明显高于脂溢性角化病(P＜0.05)；而在脂溢性角化病中的阳性表达率明显高于正常皮肤(P＜0.05)。2、端粒酶逆转录酶(hTERT)在20例脂溢性角化病皮损表达中，14例表达呈阴性，6例表达阳性，阳性率30％；20例鳞状细胞癌皮损中，10例表达呈阴性，10例表达呈阳性，阳性率50％；20例正常皮肤组织中，19例表达呈阴性，1例表达呈阳性，阳性率为5％。端粒酶逆转录酶(hTERT)在恶性皮肤肿瘤中的阳性表达率明显高于脂溢性角化病(P＜0.05)；而在脂溢性角化病中的阳性表达率明显高于正常皮肤(P＜0.05)。
结论1、磷酸化信号传导和转录激活因子PSTAT3和端粒酶逆转录酶hTERT与肿瘤的发生发展及增殖程度密切相关；2、脂溢性角化病是一种有潜在恶变倾向的良性肿瘤。
Objective To investigate the expression and significance of Signal transducer andactivator of transcription 3(PSTAT3) phosphorylation and Human TelomeraserReverse Transcriptase (hTERT) in Seborrheic Karatosis.
Methods Immunohistochemistry technique was employed to measure theexpression of PSTAT3 and hTERT in skin tissue from 20 cases of skin squamous cellcarcinoma(SCC), 20 cases of seborrhoeic keratosis(SK) and 20 normal subjects.
Results 1. 6 cases of SK and 8 cases of SCC expressed PSTAT3 protein and therewas no PSTAT3 protain expression on normal skin. Expression of PSTAT3 in SCCwas at a higher level than that of SK, also, the difference of expression of PSTAT3 hasobvious significance between SK and normal skin.2. 6 cases of SK, 10 cases of SCCand 1 case of normal skin expressed hTERT. Expression of hTERT in SCC was at ahigher level than that of SK, also, the difference of expression of PSTAT3 has obvioussignificance between SK and normal skin.
Conclusion 1. The levels of expression of PSTAT3 and hTERT was associatedclosely with the criticial stages in cutaneous tumor in development.2. seborrhoeickeratosis(SK) is a kind of benign skin tumor, but it has potential cutaneouscarcinomas formation.
引文
[1] 黄瑞雷，李远脂溢性角化病并发恶性肿瘤3例报告．中国肿瘤临床与康复 2001；8：16
[2] FERNADES A, HAMBURGER A W, GERW IN B I, etal. Erb22 k inase is required for constitutive STA T3 activation in malignant human lung epithelial cell[J]. Int J Cancer, 1999, 83: 564-570.
[3] BROMBERG J F, WRZESZCZYN SKA M H,DEV GANG, et al. STA T3 as an On cogene[J]. Cell, 1999, 98:295-303.
[4] Blakburn EH. Structure and funtion of telomeres[J]. Nature,1991, 350 (6319):569-573.
[5] Sarkar G,Bolandar ME. Telomere,telomerase and cancer[J]. Science,1995,268 (5214):1115-1117.
[6] Kyo S,Kanaya T,Takakura M, et al. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues[J]. Int J Cancer,1999,80 (1):60-63.
[7] Cascajo CD...//Am J Dermatopathol. 1996,18(3).278-282
[8] Sloan JB, Jaworsky C. Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. J Dermatol Stag Oncol 1993;19:413-416.
[9] Rao BK, Fraaman RG, Paulos EG, et al.The relationship between basal cell epithelioma and seborrheic keratosis. A study of 60 cases. J dermatol surg oncol 1994;20:761-764.
[10] 窦晓玉，方丹．21例脂溢性角化病CO2激光治疗后诱发局部糜烂和基底细胞癌．皮肤病与性病 2001；23(3)：23
[11] Herberg AJ,Garcia JA,Kerns BJ, et al. DNA ploidy of basal cell carcinoma determined by image cytometry of fresh smears. J Cutan Pathol,1993,20 (3):216～222.
[12] Prez CD,Launoit YD, Kiss R, et al. Computerized morphonuclear cell image analysis of malignant disease in bladder tissues. J Urol, 1990,143:694.
[13] Hostetter AL,Jon H,Sten OW, et al. Comparative study of DNA cytometry method for benign and malignant tissue. Am J Clin Pathol,1989,89:760.
[14] Olivia ZN. Milliman CL, Korsmcyer SJ, et al. Bcl-2 heterodimerizes invivo with a conserved homolog, bax, that accelerates programmed cell dealth,Cell. 1993,74:609
[15] 毛东军，孙咏梅等．P53、Bcl-2在皮肤鳞状细胞癌、基底细胞癌、脂溢性角化病中联合表达的意义．齐齐哈尔医学院学报 2001，22．(2)：121-122
[16] 武钦学，吴志华等．p16，p15及pRb在表皮肿瘤中的表达．国际医药卫生导报，2004，10(24)：6-8．
[1] 黄瑞雷，李远脂溢性角化病并发恶性肿瘤3例报告．中国肿瘤临床与康复 2001；8：16
[2] David Gill, Abe Dorevitch, Robin Marks.The prevalence of seborrheic keratoses in people aged 15 to 30 years, Is the term senile keratosis redundant ? Arch Dermatol 2000; 136:759-762.
[3] 高文天，李春英，黄慧．脂溢性角化病231例临床及病理分析．临床皮肤科杂志 2002；31：279-281．
[4] Tsambaos D:Monastirli A;Kparanos N,et al.Detection of human papilloma virus DNA in nongenital seborrhoeic Keratosis. Arch D ERMATOL.Res. 1995;287(6): 612-615
[5] Zhu WY, Leonardi C, Penney NS. Detectionof human papillomavirus DNA in seborrheickeratosis by polymerase chain reaction. J Dermatol Sci 1992;4: 166-171.
[6] Lee ES;Whang MR Kang WH.Absence of human papillomavirus DNA in nongenital seborrheic Keratosis by polymerase chain reaction J Dermatol Sci 1992;4(3):166-171
[7] 陈宏翔，盛晚香等．非生殖器部位脂溢性角化病皮损中HPV-DNA的检测．中华医学丛刊杂志 2002；2(9)：4-6
[8] Zhao Y Luo R;Huang X;Liu M et al. Human papilloma virus infection in seborrheic keratosis Am J Dermatopathol 11:209-212
[9] Yeatman JM, Kilkenny M, Marks R. The prevalence of seborrheic keratoses in an Australian population: dose exposure to sunlight play a part in their frequency? British J of Dermatol 1997;137:411-414.
[10] 常建民，吴意平，杨敏．老年脂溢性角化患者血脂、脂蛋白、载脂蛋白的分析．临床皮肤科杂志 2002；31：85-86．
[11] Cascajo CD...//Am J Dermatopathol. 1996,18(3).278-282
[12] Sloan JB, Jaworsky C. Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. J Dermatol Surg Oncol 1993;19:413-416.
[13] Rao BK, Fraaman RG, Paulos EG, et al.The relationship between basal cell epithelioma and seborrheic keratosis. A study of 60 cases. J dermatol surg oncol 1994;20:761-764.
[14] 窦晓玉，方丹．21例脂溢性角化病CO_2激光治疗后诱发局部糜烂和基底细胞癌．皮肤病与性病 2001；23(3)：23
[15] Herberg AJ,Garcia JA,Kerns BJ, et al. DNA ploidy of basal cell carcinoma determined by image cytometry of fresh smears. J Cutan Pathol,1993,20 (3):216～222.
[16] Prez CD,Launoit YD, Kiss R, et al. Computerized morphonuclear cell image analysis of malignant disease in bladder tissues. J Urol, 1990,143:694.
[17] Hostetter AL,Jon H,Sten OW, et al. Comparative study of DNA cytometry method for benign and malignant tissue. Am J Clin Pathol,1989,89:760.
[18] 王晓彦，萨娜，王泽民，等．鳞癌与脂溢性角化病DNA倍体图像定量分析．中国皮肤性病学杂志 2000；14：88-89．
[19] RistimakiA,SivulaA,LundinJ,etal.Prognostic significance of elevated cyclooxyg en nase-2 expression in breast cancer.CancerRes,2002,62(3):632
[20] MoranEM.Epidemiological and clinical aspects of nonsteroidal anti- inflarnmatry drugs and cancer risks. J Environ pathol Toxicl Oncol, 2002,21 (2): 193
[21] Costa C,SoaresR,Reis-FilhoJS,etal.Cyclo-oxygenase2 expression is associated with angiogenesis and lymphnode metastasis in human breast cancer. J Clin Pathol,2002,55(6):429
[22] Prescott SM,Fetzpatrick FA.Cyclooxygenase-2 and carcinogenesis. Biochem Biophys Acta,2000,1470(2):69
[23] Lou Y, Wu K,Sun A,etal.Significance of COX-1,COX-2 and iNOS expression in superificial gastritis,gastric mucosal atypical hyperplasia and gastric carcinoma,ChinJDig,2000,20(4): 223
[24] XuXC.COX-2inhibitors in cancer treatment and prevention,a recent development. Anticancer Drugs,2002,13(2):127
[25] 吴伟伟，盛晚香．脂溢性角化病皮损中还氧合酶-2蛋白的表达及其临床意义．武汉大学学报 2005，26(1)：45-47
[26] Olivia ZN. Milliman CL, Korsmcyer SJ, et al. Bcl-2 heterodimerizes invivo with a conserved homolog, bax, that accelerates programmed cell dealth,Cell. 1993,74:609
[27] 毛东军，孙咏梅等．P~(53)、Bcl-2在皮肤鳞状细胞癌、基底细胞癌、脂溢性角化病中联合表达的意义．齐齐哈尔医学院学报 2001，22(2)：121-122
[28] Geradts J.,Kratzke RA.,Niehans GA., et al. lmmuno-histochemical detectionof cyclin-dependent kinase inhibitor 2/Multiple tumor suppressor gene 1 (CDNK2/MTS1) product p16INK4A in archival human solid tumor:Correlation with retinoblastoma protein expression.Cancer Res, 1995,55(24):6006-6011
[29] Shapiro GI., Edwards CD., Kobzik L., et al. Reciprocal Rb inactivation and p16INK4 expression in primary lung cancer and cell lines. Cancer Res, 1995;55:505-509
[30] 武钦学，吴志华等．p16，p15及pRb在表皮肿瘤中的表达．国际医药卫生导报，2004，10(24)：6-8．
31 Blakburn EH. Structure and funtion of telomeres[J]. Nature,1991, 350 (6319):569-573.
[32] Sarkar G, Bolandar ME. Telomere,telomerase and cancer[J]. Science,1995,268 (5214):1115-1117.
[33] Kyo S,Kanaya T, Takakura M, et al. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues[J]. Int J Cancer,1999,80 (1):60-63.
[34] 丁颖果，武玲慎，涂平．端粒酶逆转录酶在皮肤肿瘤原位表达水平的比较．中国皮肤性病学杂志，2004，18(1)：8-10．
[35] FERNADES A, HAMBURGER A W, GERW IN B I, etal. Erb22 k inase is required for constitutive STA T3 activation in malignant human lung epithelial cell[J]. Int J Cancer, 1999, 83: 564-570.
[36] BROMBERG J F,WRZESZCZYN SKA M H,DEV GANG, et al. STA T3 as an On cogene[J]. Cell, 1999, 98:295-303.
[37] 蔡绥，陈丽荣，王海军，等．磷酸化STAT3和p53基因在表皮肿瘤的表达．浙江大学学报(医学版)2004；33：331-334
[38] 沈宏，张晴，许爱娥，施源胎盘型谷胱甘肽转换酶在皮肤角朊细胞肿瘤中的表达．临床皮肤科杂志 1998；10：27：300-302
[39] Hanada K, Ishikawa H, Tamaik,et al. Expression of glutat hione S2t rans ferase-π in malignant skin tumors J Dermatol Sci, 1991,2: 18.
[40] Zhang L, Xiao Y, Priddy R. Increase in placental glutat hionS2transferase in human oral epithelial dysplastic lesions andsquamous cell carcinomas. J Oral Pat hol Med,1994,23: 75.
[41] Carder PJ, Al2Naf ussi A, Rahilly M, et al. Glutat hioneSt ransferase detoxification enzymes in cercical neoplasia. J Pat hol, 1990,162: 303.
[42] Thomas DJ, Birch PJ, Vickers J,et al. Glutathione S2t ransferase-π expression in transitional cell carcinoma of the bladder. Br J Urology, 1993,72: 740.
[43] Amagai M, Autoimmunity against desmosomal cadherinsinpemphi2gus. Jdermato Sci 1999;20:92-102.
[44] 韩钢文，汤占利，涂平．桥粒芯糖蛋白1和2在不同表皮肿瘤中的表达．中华皮肤科杂志 2002；35：439-441．
[45] 汤占利，韩钢文，涂平．皮肤基底细胞癌组织中桥粒芯糖蛋白1+2表达的研究．临床皮肤科杂志 2003；32：252-253．
[46] 葛新红，涂平等．桥粒芯糖蛋白1在不同表皮肿瘤中表达的研究．中国麻风皮肤病学杂志 2004；20：421-423
[47] Miyauchi T, Kanekura T, Yamaoka A, et al. Basigin, a new,broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin V domain and the beta-chain of major histocompatibility complex class Ⅱ antigen.J Biochem(Tokyo), 1990,107:316-323.
[48] Spring FA, Homes CH, Simpson KL, et al. The Oka blood group antigen is a marker for the M6 leukocyte activation antigen, the human homolog of OX-47 antigen,basigen and neurothelin, an immuoglobulin superfamily molecule that is widely expressed in human cells and tissues. Eur J Immunol, 1997,27:891-897.
[49] Igakura T, Kadomatsu K, Kaname T, et al. A null mutation in basigin, an immuno globulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol, 1998, 194:152-165
[50] 陈翔，李吉等．CD147在角质形成细胞分化过程中的表达和作用中华皮肤科杂志 2003；36：318-321
[51] Shin EC, Ahn JM, Kim CH, et al. IFN-gamma induces cell death in human hepatoma cells through a TRAIL/death receptor-mediated apoptotic pathway. Int J Cancer 2001;93:262.
[52] Ruiz-Ruiz C, Munoz-Pinedo C, Lopez-Rivas A. Interferon-gamma treatment elevates caspase-8 expression and sensitizes human breast tumor cells to a death receptor-induced mitochondria-operated apoptotic program. Cancer Res 2000;60:5673.
[53] 樊翌明等．某些表皮肿瘤中干扰素r表达及其与临床病理特征的关系．中国麻风皮肤病杂志 2004；20：312-314．
[54] 周光飚．Caspases家族与细胞凋亡调控．国外医学分子生物学分册 2000；22：167-170．
[55] 张春玲，葛蒙梁．细胞凋亡在脂溢性角化病中的作用 2004，20：336-337．
[56] PesceC,ScanloraS.Apoptosisintheareaofsquamousdifferentiationirritatedsebor rheickeratosis.J Cutan Pathol 2000;27:121-123.
[57] Maria RS, Maria SB, Giovanna M, et, al. Increased c-myconogene expression in ewing's sarcome:correlation with Ki67 proliferation index. Tumor, 1999,85:167-173.
[58] 李澄，樊小妹等．皮肤良恶性肿瘤中p16、p21~(ras)和ki-67蛋白表达研究．岭南皮肤性病科杂志 2002；9：77-81．
[59] CiardiellaF, KimN,McGeadyML,etal.Expressionoftransforminggrowthfactoral pha (TGFalpha)inbreastcancer.AnnOncol, 1991,2(3): 169
[60] Iitakura Y, Sasano H,Shiga C, et al. Epidermal growth actor receptor over expression in esophageal carcinoma.Cancer, 1994,74:795
[61] 王军琳，刘源，金岩，吕红兵，赵宇，王新文，董蕊．EGF对真皮成纤维细胞中cyclinD1和CDK24表达的影响[J]．第四军医大学学报，2002；23(10)：935-938．
[62] 孙林潮，刘玉峰，刘彦仿，张泰山．抗角蛋白自身抗体对无血清培养黑素细胞及角质形成细胞增殖的影响[J]．第四军医大学学报，2001；22(24)：2220-2222．
[63] 万福印，赵群力等．脂溢性角化病皮肤EGF的表达．第四军医大学学报，2003；24(17)：1619-1621．
[64] 肖汉龙，盛晚香等．脂溢性角化病中TGF-a及EGFr的表达武汉大学学报，2004：25：309-310．
[65] Li CX,Wan YH,Chi SM, etal. Purificatio of natural antikeratinau 2 to anti bodies from normal human serum and their effecton human keratino cytes culture dinvitro[J]. Br JD ermatol, 2001,145(5):737-748.
[66] 王刚，刘玉峰．抗角蛋白自身抗体的研究现状与展望[J]．中国皮肤性病学杂志，2000，14(1)：49-50．
[67] 王刚，刘玉峰，刘彦仿．抗角蛋白自身抗体对培养角朊细胞代谢活性的影响[J]．中华皮肤科杂志，1994，27(2)：94-95．
[68] 王刚，刘玉峰，刘彦仿．银屑病血清抗角蛋白自身抗体对角朊细胞代谢的作用[J]．中国皮肤性病学杂志，1995，9(1)：16-17．
[69] 卢宁，王刚等．基因工程抗角蛋白抗体在正常皮肤和几种表皮增生性皮肤病皮损中的反应定位．中国皮肤性病学杂志 2003，17(4)：221-223．
[70] 谢朝阳，祝其锋．细胞周期调控与阿尔茨海默病的研究进展[J]．中国老年学杂志，2004，4：379
[71] Balasubramanian S,Ahmad N,Jeedigunta S, et al. Alteration sin cell cycle regulation in mo use skin tumors[J]. Biochem Biophys Res Commun, 1998,243(3):744
[72] 陈旭娥，盛晚香．P21~(WAF1/CIP1)和细胞周期蛋白E在脂溢性角化病中的表达及意义．实用诊断与治疗杂志，2005，19(3)：160-161．
[73] Karsunky H,Geisen C,Schmidt T, et al. Oncogenic potential of cyclin EinT celllymp homa genesis intrans genic mice: evidence for coorperation between cyclin Eand Rasbutnot Myc[J]. Oncogene, 1999,18(54):7816
[74] 蔓小红，王家璧，刘跃华，等．细胞周期蛋白E和p27在鲍温样丘疹病和外生殖器表皮原位癌中的作用[J]．临床皮肤科杂志，2003，32(9)：515
[75] 沈宏，许爱娥．p27!细胞周期素E!p21在角化棘皮瘤皮损中的表达[J]．中华皮肤科杂志，2002，35(1)：51
[76] Lee SC, Lee JB, Seo JJ. et al. Expression of trichohyalin in dermatological disorder. A comparative study with involucrin and filaggrin immunohisto chemical staining. Acta Derm Venereol 1999;79:97.
[77] Sumitono S, Kumasa S, Iwai Y. et al. Involucr in expression in epithelial,tumor of oral and pharyngeal mucosa and skin. Oral Surgoral Med Oral Pathol 1986;62:63.
[78] Fujisawa H, Naito Y, Muraki R, et al. Dif2ferentiation disorders of keratinocytes in se2 borrheic keratosis (acanthotic type). J Der2matol 1991;18:635-638.
[79] Luzi P, Miracco C, Del Vecchio MT. Stereologicalstudy of desmosomes in basal cell carcinama and seborrheic keratosis. J SubmicroscCytol 1987;19:337-343.
[80] Manaka L , Kadono S , Kawashima M, elal ,The mechanism of hyperpigmentation in seborrheic keratosis involves the high expression of endothelin - converting enzyme - l alpha and TNF - alpha ,which stimulate secretion of endothelin 1. Br J Dermatol 2001 ;145 :895-903.
[2] FERNADES A, HAMBURGER A W, GERW IN B I, etal. Erb22 k inase is required for constitutive STA T3 activation in malignant human lung epithelial cell[J]. Int J Cancer, 1999, 83: 564-570.
[3] BROMBERG J F, WRZESZCZYN SKA M H,DEV GANG, et al. STA T3 as an On cogene[J]. Cell, 1999, 98:295-303.
[4] Blakburn EH. Structure and funtion of telomeres[J]. Nature,1991, 350 (6319):569-573.
[5] Sarkar G,Bolandar ME. Telomere,telomerase and cancer[J]. Science,1995,268 (5214):1115-1117.
[6] Kyo S,Kanaya T,Takakura M, et al. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues[J]. Int J Cancer,1999,80 (1):60-63.
[7] Cascajo CD...//Am J Dermatopathol. 1996,18(3).278-282
[8] Sloan JB, Jaworsky C. Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. J Dermatol Stag Oncol 1993;19:413-416.
[9] Rao BK, Fraaman RG, Paulos EG, et al.The relationship between basal cell epithelioma and seborrheic keratosis. A study of 60 cases. J dermatol surg oncol 1994;20:761-764.
[10] 窦晓玉，方丹．21例脂溢性角化病CO2激光治疗后诱发局部糜烂和基底细胞癌．皮肤病与性病 2001；23(3)：23
[11] Herberg AJ,Garcia JA,Kerns BJ, et al. DNA ploidy of basal cell carcinoma determined by image cytometry of fresh smears. J Cutan Pathol,1993,20 (3):216～222.
[12] Prez CD,Launoit YD, Kiss R, et al. Computerized morphonuclear cell image analysis of malignant disease in bladder tissues. J Urol, 1990,143:694.
[13] Hostetter AL,Jon H,Sten OW, et al. Comparative study of DNA cytometry method for benign and malignant tissue. Am J Clin Pathol,1989,89:760.
[14] Olivia ZN. Milliman CL, Korsmcyer SJ, et al. Bcl-2 heterodimerizes invivo with a conserved homolog, bax, that accelerates programmed cell dealth,Cell. 1993,74:609
[15] 毛东军，孙咏梅等．P53、Bcl-2在皮肤鳞状细胞癌、基底细胞癌、脂溢性角化病中联合表达的意义．齐齐哈尔医学院学报 2001，22．(2)：121-122
[16] 武钦学，吴志华等．p16，p15及pRb在表皮肿瘤中的表达．国际医药卫生导报，2004，10(24)：6-8．
[1] 黄瑞雷，李远脂溢性角化病并发恶性肿瘤3例报告．中国肿瘤临床与康复 2001；8：16
[2] David Gill, Abe Dorevitch, Robin Marks.The prevalence of seborrheic keratoses in people aged 15 to 30 years, Is the term senile keratosis redundant ? Arch Dermatol 2000; 136:759-762.
[3] 高文天，李春英，黄慧．脂溢性角化病231例临床及病理分析．临床皮肤科杂志 2002；31：279-281．
[4] Tsambaos D:Monastirli A;Kparanos N,et al.Detection of human papilloma virus DNA in nongenital seborrhoeic Keratosis. Arch D ERMATOL.Res. 1995;287(6): 612-615
[5] Zhu WY, Leonardi C, Penney NS. Detectionof human papillomavirus DNA in seborrheickeratosis by polymerase chain reaction. J Dermatol Sci 1992;4: 166-171.
[6] Lee ES;Whang MR Kang WH.Absence of human papillomavirus DNA in nongenital seborrheic Keratosis by polymerase chain reaction J Dermatol Sci 1992;4(3):166-171
[7] 陈宏翔，盛晚香等．非生殖器部位脂溢性角化病皮损中HPV-DNA的检测．中华医学丛刊杂志 2002；2(9)：4-6
[8] Zhao Y Luo R;Huang X;Liu M et al. Human papilloma virus infection in seborrheic keratosis Am J Dermatopathol 11:209-212
[9] Yeatman JM, Kilkenny M, Marks R. The prevalence of seborrheic keratoses in an Australian population: dose exposure to sunlight play a part in their frequency? British J of Dermatol 1997;137:411-414.
[10] 常建民，吴意平，杨敏．老年脂溢性角化患者血脂、脂蛋白、载脂蛋白的分析．临床皮肤科杂志 2002；31：85-86．
[11] Cascajo CD...//Am J Dermatopathol. 1996,18(3).278-282
[12] Sloan JB, Jaworsky C. Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. J Dermatol Surg Oncol 1993;19:413-416.
[13] Rao BK, Fraaman RG, Paulos EG, et al.The relationship between basal cell epithelioma and seborrheic keratosis. A study of 60 cases. J dermatol surg oncol 1994;20:761-764.
[14] 窦晓玉，方丹．21例脂溢性角化病CO_2激光治疗后诱发局部糜烂和基底细胞癌．皮肤病与性病 2001；23(3)：23
[15] Herberg AJ,Garcia JA,Kerns BJ, et al. DNA ploidy of basal cell carcinoma determined by image cytometry of fresh smears. J Cutan Pathol,1993,20 (3):216～222.
[16] Prez CD,Launoit YD, Kiss R, et al. Computerized morphonuclear cell image analysis of malignant disease in bladder tissues. J Urol, 1990,143:694.
[17] Hostetter AL,Jon H,Sten OW, et al. Comparative study of DNA cytometry method for benign and malignant tissue. Am J Clin Pathol,1989,89:760.
[18] 王晓彦，萨娜，王泽民，等．鳞癌与脂溢性角化病DNA倍体图像定量分析．中国皮肤性病学杂志 2000；14：88-89．
[19] RistimakiA,SivulaA,LundinJ,etal.Prognostic significance of elevated cyclooxyg en nase-2 expression in breast cancer.CancerRes,2002,62(3):632
[20] MoranEM.Epidemiological and clinical aspects of nonsteroidal anti- inflarnmatry drugs and cancer risks. J Environ pathol Toxicl Oncol, 2002,21 (2): 193
[21] Costa C,SoaresR,Reis-FilhoJS,etal.Cyclo-oxygenase2 expression is associated with angiogenesis and lymphnode metastasis in human breast cancer. J Clin Pathol,2002,55(6):429
[22] Prescott SM,Fetzpatrick FA.Cyclooxygenase-2 and carcinogenesis. Biochem Biophys Acta,2000,1470(2):69
[23] Lou Y, Wu K,Sun A,etal.Significance of COX-1,COX-2 and iNOS expression in superificial gastritis,gastric mucosal atypical hyperplasia and gastric carcinoma,ChinJDig,2000,20(4): 223
[24] XuXC.COX-2inhibitors in cancer treatment and prevention,a recent development. Anticancer Drugs,2002,13(2):127
[25] 吴伟伟，盛晚香．脂溢性角化病皮损中还氧合酶-2蛋白的表达及其临床意义．武汉大学学报 2005，26(1)：45-47
[26] Olivia ZN. Milliman CL, Korsmcyer SJ, et al. Bcl-2 heterodimerizes invivo with a conserved homolog, bax, that accelerates programmed cell dealth,Cell. 1993,74:609
[27] 毛东军，孙咏梅等．P~(53)、Bcl-2在皮肤鳞状细胞癌、基底细胞癌、脂溢性角化病中联合表达的意义．齐齐哈尔医学院学报 2001，22(2)：121-122
[28] Geradts J.,Kratzke RA.,Niehans GA., et al. lmmuno-histochemical detectionof cyclin-dependent kinase inhibitor 2/Multiple tumor suppressor gene 1 (CDNK2/MTS1) product p16INK4A in archival human solid tumor:Correlation with retinoblastoma protein expression.Cancer Res, 1995,55(24):6006-6011
[29] Shapiro GI., Edwards CD., Kobzik L., et al. Reciprocal Rb inactivation and p16INK4 expression in primary lung cancer and cell lines. Cancer Res, 1995;55:505-509
[30] 武钦学，吴志华等．p16，p15及pRb在表皮肿瘤中的表达．国际医药卫生导报，2004，10(24)：6-8．
31 Blakburn EH. Structure and funtion of telomeres[J]. Nature,1991, 350 (6319):569-573.
[32] Sarkar G, Bolandar ME. Telomere,telomerase and cancer[J]. Science,1995,268 (5214):1115-1117.
[33] Kyo S,Kanaya T, Takakura M, et al. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues[J]. Int J Cancer,1999,80 (1):60-63.
[34] 丁颖果，武玲慎，涂平．端粒酶逆转录酶在皮肤肿瘤原位表达水平的比较．中国皮肤性病学杂志，2004，18(1)：8-10．
[35] FERNADES A, HAMBURGER A W, GERW IN B I, etal. Erb22 k inase is required for constitutive STA T3 activation in malignant human lung epithelial cell[J]. Int J Cancer, 1999, 83: 564-570.
[36] BROMBERG J F,WRZESZCZYN SKA M H,DEV GANG, et al. STA T3 as an On cogene[J]. Cell, 1999, 98:295-303.
[37] 蔡绥，陈丽荣，王海军，等．磷酸化STAT3和p53基因在表皮肿瘤的表达．浙江大学学报(医学版)2004；33：331-334
[38] 沈宏，张晴，许爱娥，施源胎盘型谷胱甘肽转换酶在皮肤角朊细胞肿瘤中的表达．临床皮肤科杂志 1998；10：27：300-302
[39] Hanada K, Ishikawa H, Tamaik,et al. Expression of glutat hione S2t rans ferase-π in malignant skin tumors J Dermatol Sci, 1991,2: 18.
[40] Zhang L, Xiao Y, Priddy R. Increase in placental glutat hionS2transferase in human oral epithelial dysplastic lesions andsquamous cell carcinomas. J Oral Pat hol Med,1994,23: 75.
[41] Carder PJ, Al2Naf ussi A, Rahilly M, et al. Glutat hioneSt ransferase detoxification enzymes in cercical neoplasia. J Pat hol, 1990,162: 303.
[42] Thomas DJ, Birch PJ, Vickers J,et al. Glutathione S2t ransferase-π expression in transitional cell carcinoma of the bladder. Br J Urology, 1993,72: 740.
[43] Amagai M, Autoimmunity against desmosomal cadherinsinpemphi2gus. Jdermato Sci 1999;20:92-102.
[44] 韩钢文，汤占利，涂平．桥粒芯糖蛋白1和2在不同表皮肿瘤中的表达．中华皮肤科杂志 2002；35：439-441．
[45] 汤占利，韩钢文，涂平．皮肤基底细胞癌组织中桥粒芯糖蛋白1+2表达的研究．临床皮肤科杂志 2003；32：252-253．
[46] 葛新红，涂平等．桥粒芯糖蛋白1在不同表皮肿瘤中表达的研究．中国麻风皮肤病学杂志 2004；20：421-423
[47] Miyauchi T, Kanekura T, Yamaoka A, et al. Basigin, a new,broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin V domain and the beta-chain of major histocompatibility complex class Ⅱ antigen.J Biochem(Tokyo), 1990,107:316-323.
[48] Spring FA, Homes CH, Simpson KL, et al. The Oka blood group antigen is a marker for the M6 leukocyte activation antigen, the human homolog of OX-47 antigen,basigen and neurothelin, an immuoglobulin superfamily molecule that is widely expressed in human cells and tissues. Eur J Immunol, 1997,27:891-897.
[49] Igakura T, Kadomatsu K, Kaname T, et al. A null mutation in basigin, an immuno globulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol, 1998, 194:152-165
[50] 陈翔，李吉等．CD147在角质形成细胞分化过程中的表达和作用中华皮肤科杂志 2003；36：318-321
[51] Shin EC, Ahn JM, Kim CH, et al. IFN-gamma induces cell death in human hepatoma cells through a TRAIL/death receptor-mediated apoptotic pathway. Int J Cancer 2001;93:262.
[52] Ruiz-Ruiz C, Munoz-Pinedo C, Lopez-Rivas A. Interferon-gamma treatment elevates caspase-8 expression and sensitizes human breast tumor cells to a death receptor-induced mitochondria-operated apoptotic program. Cancer Res 2000;60:5673.
[53] 樊翌明等．某些表皮肿瘤中干扰素r表达及其与临床病理特征的关系．中国麻风皮肤病杂志 2004；20：312-314．
[54] 周光飚．Caspases家族与细胞凋亡调控．国外医学分子生物学分册 2000；22：167-170．
[55] 张春玲，葛蒙梁．细胞凋亡在脂溢性角化病中的作用 2004，20：336-337．
[56] PesceC,ScanloraS.Apoptosisintheareaofsquamousdifferentiationirritatedsebor rheickeratosis.J Cutan Pathol 2000;27:121-123.
[57] Maria RS, Maria SB, Giovanna M, et, al. Increased c-myconogene expression in ewing's sarcome:correlation with Ki67 proliferation index. Tumor, 1999,85:167-173.
[58] 李澄，樊小妹等．皮肤良恶性肿瘤中p16、p21~(ras)和ki-67蛋白表达研究．岭南皮肤性病科杂志 2002；9：77-81．
[59] CiardiellaF, KimN,McGeadyML,etal.Expressionoftransforminggrowthfactoral pha (TGFalpha)inbreastcancer.AnnOncol, 1991,2(3): 169
[60] Iitakura Y, Sasano H,Shiga C, et al. Epidermal growth actor receptor over expression in esophageal carcinoma.Cancer, 1994,74:795
[61] 王军琳，刘源，金岩，吕红兵，赵宇，王新文，董蕊．EGF对真皮成纤维细胞中cyclinD1和CDK24表达的影响[J]．第四军医大学学报，2002；23(10)：935-938．
[62] 孙林潮，刘玉峰，刘彦仿，张泰山．抗角蛋白自身抗体对无血清培养黑素细胞及角质形成细胞增殖的影响[J]．第四军医大学学报，2001；22(24)：2220-2222．
[63] 万福印，赵群力等．脂溢性角化病皮肤EGF的表达．第四军医大学学报，2003；24(17)：1619-1621．
[64] 肖汉龙，盛晚香等．脂溢性角化病中TGF-a及EGFr的表达武汉大学学报，2004：25：309-310．
[65] Li CX,Wan YH,Chi SM, etal. Purificatio of natural antikeratinau 2 to anti bodies from normal human serum and their effecton human keratino cytes culture dinvitro[J]. Br JD ermatol, 2001,145(5):737-748.
[66] 王刚，刘玉峰．抗角蛋白自身抗体的研究现状与展望[J]．中国皮肤性病学杂志，2000，14(1)：49-50．
[67] 王刚，刘玉峰，刘彦仿．抗角蛋白自身抗体对培养角朊细胞代谢活性的影响[J]．中华皮肤科杂志，1994，27(2)：94-95．
[68] 王刚，刘玉峰，刘彦仿．银屑病血清抗角蛋白自身抗体对角朊细胞代谢的作用[J]．中国皮肤性病学杂志，1995，9(1)：16-17．
[69] 卢宁，王刚等．基因工程抗角蛋白抗体在正常皮肤和几种表皮增生性皮肤病皮损中的反应定位．中国皮肤性病学杂志 2003，17(4)：221-223．
[70] 谢朝阳，祝其锋．细胞周期调控与阿尔茨海默病的研究进展[J]．中国老年学杂志，2004，4：379
[71] Balasubramanian S,Ahmad N,Jeedigunta S, et al. Alteration sin cell cycle regulation in mo use skin tumors[J]. Biochem Biophys Res Commun, 1998,243(3):744
[72] 陈旭娥，盛晚香．P21~(WAF1/CIP1)和细胞周期蛋白E在脂溢性角化病中的表达及意义．实用诊断与治疗杂志，2005，19(3)：160-161．
[73] Karsunky H,Geisen C,Schmidt T, et al. Oncogenic potential of cyclin EinT celllymp homa genesis intrans genic mice: evidence for coorperation between cyclin Eand Rasbutnot Myc[J]. Oncogene, 1999,18(54):7816
[74] 蔓小红，王家璧，刘跃华，等．细胞周期蛋白E和p27在鲍温样丘疹病和外生殖器表皮原位癌中的作用[J]．临床皮肤科杂志，2003，32(9)：515
[75] 沈宏，许爱娥．p27!细胞周期素E!p21在角化棘皮瘤皮损中的表达[J]．中华皮肤科杂志，2002，35(1)：51
[76] Lee SC, Lee JB, Seo JJ. et al. Expression of trichohyalin in dermatological disorder. A comparative study with involucrin and filaggrin immunohisto chemical staining. Acta Derm Venereol 1999;79:97.
[77] Sumitono S, Kumasa S, Iwai Y. et al. Involucr in expression in epithelial,tumor of oral and pharyngeal mucosa and skin. Oral Surgoral Med Oral Pathol 1986;62:63.
[78] Fujisawa H, Naito Y, Muraki R, et al. Dif2ferentiation disorders of keratinocytes in se2 borrheic keratosis (acanthotic type). J Der2matol 1991;18:635-638.
[79] Luzi P, Miracco C, Del Vecchio MT. Stereologicalstudy of desmosomes in basal cell carcinama and seborrheic keratosis. J SubmicroscCytol 1987;19:337-343.
[80] Manaka L , Kadono S , Kawashima M, elal ,The mechanism of hyperpigmentation in seborrheic keratosis involves the high expression of endothelin - converting enzyme - l alpha and TNF - alpha ,which stimulate secretion of endothelin 1. Br J Dermatol 2001 ;145 :895-903.