p27和Skp2在人睾丸生殖细胞肿瘤中的表达和意义
摘要
目的：1．检测细胞周期素依赖激酶抑制蛋白p27和S期激酶相关蛋白2(Skp2)在睾丸生殖细胞肿瘤、正常睾丸和慢性睾丸炎中的蛋白质表达的差异；2．探讨p27和Skp2表达与睾丸生殖细胞肿瘤临床分期、病理分级等预后影响因素之间的关系；3．分析p27和Skp2在睾丸生殖细胞肿瘤中表达的相关性。
方法：采用免疫组化S-P法对55例睾丸生殖细胞肿瘤，10例正常睾丸组织和10例慢性睾丸炎组织中的p27和Skp2的表达情况进行了检测，并对不同临床病理特征的睾丸生殖细胞肿瘤中的p27和Skp2表达进行分析比较。
结果：1．p27在55例睾丸生殖细胞肿瘤中阳性表达26例，阳性表达率为47.3％，平均免疫反应积分(IRS)为1.27±1.54；在正常睾丸组织中阳性表达9例，阳性表达率为90.0％，IRS为4.66±2.17；慢性睾丸炎组织中阳性表达8例，阳性表达率为80.0％，IRS为3.76±2.52，睾丸生殖细胞肿瘤中p27阳性表达率和表达强度与正常睾丸组织和慢性睾丸炎组织相比明显降低，差异具有显著性(P＜0.05)。Skp2在55例睾丸生殖细胞肿瘤中阳性表达41例，阳性表达率为74.5％，IRS为2.89±1.91；在正常睾丸组织中阳性表达2例，阳性表达率为20.0％，IRS为0.28±0.62；
Objectives: 1. To detect the differences of a cyclin-dependent kinase
inhibitory protein p27 and S-phase kinase-associated protein 2(Skp2) expression among human testicular germ cell tumors, normal testicle and chronic orchitis. 2. To investigate the relation of p27 and Skp2 expression with the clinical stage and patho-grade of human testicular germ cell tumors. 3. To analyze the correlation between expression of p27 and Skp2 in human testicular germ cell tumors.
Methods: p27 and Skp2 protein expression were evaluated in the tissues of
55 human testicular germ cell tumors and 10 normal testicular, 10 chronic orchitis using immunohistochemistry (S-Pmethod). The immunoreactivity of p27 and Skp2 was analyzed with respect to associations with clinical stage and patho-grade of human testicular germ cell tumors.
Results: 1. Among the 55 testicular germ cell tumors, 26 cases showed
positive staining of the p27, positive rate 47.3%, immunoreactive score(IRS) was 1.27±1.54, and 9 cases showed positive staining of the p27 in 10 normal testicular, positive rate 90.0%, IRS was 4.66 ± 2.17, 8 cases showed positive staining of the p27 in chronic orchitis, positive rate 80.0%, IRS was 3.76 ± 2.52. There was a significant difference of the p27 expression between testicular germ cell tumor and normal testicular or chronic orchitis (P<0.05).
方法：采用免疫组化S-P法对55例睾丸生殖细胞肿瘤，10例正常睾丸组织和10例慢性睾丸炎组织中的p27和Skp2的表达情况进行了检测，并对不同临床病理特征的睾丸生殖细胞肿瘤中的p27和Skp2表达进行分析比较。
结果：1．p27在55例睾丸生殖细胞肿瘤中阳性表达26例，阳性表达率为47.3％，平均免疫反应积分(IRS)为1.27±1.54；在正常睾丸组织中阳性表达9例，阳性表达率为90.0％，IRS为4.66±2.17；慢性睾丸炎组织中阳性表达8例，阳性表达率为80.0％，IRS为3.76±2.52，睾丸生殖细胞肿瘤中p27阳性表达率和表达强度与正常睾丸组织和慢性睾丸炎组织相比明显降低，差异具有显著性(P＜0.05)。Skp2在55例睾丸生殖细胞肿瘤中阳性表达41例，阳性表达率为74.5％，IRS为2.89±1.91；在正常睾丸组织中阳性表达2例，阳性表达率为20.0％，IRS为0.28±0.62；
Objectives: 1. To detect the differences of a cyclin-dependent kinase
inhibitory protein p27 and S-phase kinase-associated protein 2(Skp2) expression among human testicular germ cell tumors, normal testicle and chronic orchitis. 2. To investigate the relation of p27 and Skp2 expression with the clinical stage and patho-grade of human testicular germ cell tumors. 3. To analyze the correlation between expression of p27 and Skp2 in human testicular germ cell tumors.
Methods: p27 and Skp2 protein expression were evaluated in the tissues of
55 human testicular germ cell tumors and 10 normal testicular, 10 chronic orchitis using immunohistochemistry (S-Pmethod). The immunoreactivity of p27 and Skp2 was analyzed with respect to associations with clinical stage and patho-grade of human testicular germ cell tumors.
Results: 1. Among the 55 testicular germ cell tumors, 26 cases showed
positive staining of the p27, positive rate 47.3%, immunoreactive score(IRS) was 1.27±1.54, and 9 cases showed positive staining of the p27 in 10 normal testicular, positive rate 90.0%, IRS was 4.66 ± 2.17, 8 cases showed positive staining of the p27 in chronic orchitis, positive rate 80.0%, IRS was 3.76 ± 2.52. There was a significant difference of the p27 expression between testicular germ cell tumor and normal testicular or chronic orchitis (P<0.05).
引文
1．吴在德，吴肇汉主编．外科学．人民卫生出版社．2003：716-717。
2. Ginsburg J. Unanswered questions in carcinoma of the testis. The Lancet. 1997, 349: 1785-1786.
3．郭应禄，辛钟成主编．男子生殖医学．北京医科大学出版社．2002：159。
4．吴阶平主编．吴阶平泌尿外科学．山东科学技术出版社．2003：993。
5. Poata F, Vecci AM, Graroato AM, et al. P27 expression in normal epithelium benign and neoplastic breast veisons. J Pathol, 2002, 196(1): 26.
6. Loda M, Cukor B, Tam SW, et al. Increased proteasome-dependent degradation of The cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med, 1997, 3(2): 231-234.
7. Yang G, Ayala G, Marzo AD, et al. Elevated skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clinical CancerResearch, 2002, 8(11): 3419-3426.
8. Tsukamoto S, Sugio K, Sakada T, et al. Reduced expression of cell-cycle regulator p27 correlates with a shortened survival in non-small cells lung cancer. Lung Cancer, 2001, 34(1): 83-90.
9. Kuo MY, Hsu HY, Kok SH, et al. Prognostic role of p27 expression in oral squamous cell carcinoma in Taiman. Oroal Oncol, 2002, 38(2): 172.
10. Masuda M, Takano Y, Iki AM, et al. Cyclin-dependent kinase inhibitor P27kipl expression in transitional cell carcinoma of renal pelvis and ureter. Cancer Letters,2000,150(2):183-189.
11. Langner C, Wasielewski R,Ratschek M,et al.Biological significance of p27 and Skp2 expression in renal cell carcinoma.A systemati systematic analysis of primary and metastatic tumor tissues using a tissue microarray technique.Virchows Archiv,2004,445 (6):631- 636.
12. Signoretti S,Di Marcotullio L,Richardson A,et al. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. Clin Invest2002, 110(5): 633-641.
13. Yang G, Ayala G, Marzo AD, et al. Elevated skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clinical Cancer Research, 2002, 8(11):3419-3426.
14. Shirane M,Harumiyal Y,Ishida H,et al.Down-regulation of p27 by two mechanisms Ubiquitin-mediated degradation and proteolytic processing. J Biol chem 1999,274(20): 13886-13893.
15. Renmmele W, Stegner HE.Recommendation for uniform definition of antimmunoreactive score(IRS) for immunohistochemical estrogen receptordection (ER-CIA) in brest cancer tissue.Pathologe 1987, 8(1): 138-140.
16. Pietenpol JA, BohlanderSK, Sato Y, etal. Assignment of the human p27 gene to 12p and its analysis in leukemias. Cancer Res, 1995, 55(6):1206-1210.
17. Ponce Castaneda MV, Lee MH , Latres E, et al. p27 chromosomal mapping to 12p12-12p13. 1 and absence of mutations in human tumors. Cancer Res, 1995, 55(6):1211-1214.
18. 王华,王靖花.p27与肿瘤.中华病理学杂志, 1999, 28(2):140-142.
19. Kawamata N, Morosetti R, Miller CW , et al. Molecular analysis of the cyclin-dependent kinase inhibitor gene p27 in human malignancies. Cancer Res, 1995, 55(11):2266-2269.
20. Lloyd RV, Jin L, Qian X, etal. Aberrant p27 expression in endocrine and other tumors. Am J Pathol, 1997, 150(2):401-407.
21. Esposito V, Baldi A, DeLuca A, etal. Prognostic role of the cyclin- dependent kinase inhibitor p27 in non-small cell lung cancer.Cancer Res, 1997, 57(16):3381-3385.
22. LodaM, CukorB, Tam SW, etal. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive coloretal carcinomas. Nat Med, 1997, 3(2):231-234.
23. Yasui W, Kudo Y, Semba S, et al. Reduced expression of cyclin dependent kinase inhibitor p27 is associated with advanced stage and invasiveness of gastric carcinomas. Jpn J Cancer Res, 1997, 88(7):625-629.
24. Zi X, Adam WG,Hsing JK, et al.A flavonoid antioxidant,silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors,G_1 arrest,and anticarcinogenic effects in human prostate carcinoma DU145 cells.Cancer Res, 1998,58(9): 1920-1923.
25. Zhang JH, Wang XF, Ye HY, et al. Expression of p27 protein and cyclinD1 protein in renal cell carcinomaion. Chin J Urol, 2001,22 (5): 264-266.
26. Lioyd RV,Jin L,Qian X et al.Aberrant p27 expression in endocrine and other tumors.Am J Pathol,1997,151(3):401-407.
27. Langner C, von Wasielewski R et al. Expression of p27 and its ubiquitin ligase subunit Skp2 in upper urinary tract transitional cell carcinoma. Uro logy, 2004, 64(3): 611-616.
28. Masuda M, Takano Y, Iki AM, et al. Cyclin-dependent kinase inhibitor P27 expression in transitional cell carcinoma of renal pelvis and ureter. Cancer Letters, 2000, 150: 183-189.
29. Feakins RM, Muleahy HE, Quaglia A, et al. p27 loss does not predict survival in patients with advanced gastric carcinoma. Cancer, 2000, 89(8): 1684-1691.
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35．吕会增，朱晓峰，等．Skp2、p27蛋白表达与胃癌的临床关系．中国医师杂志，2005，7(6)：751-753．
36. Shirane M, Harumiyal Y, Ishida N, et al. Down-regulation of p27 by two mechanisms, ubiquitin-mediated degradation and proteolytic processing. The Journal of biological chemistry, 1999, 274(20): 13886-13893.
37. Ben-Izhak O, Lahaz-Baratz S, Meretyk S, et al. Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27 in prostate cancer. Urol, 170(2): 241-245, 2003.
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2. Ginsburg J. Unanswered questions in carcinoma of the testis. The Lancet. 1997, 349: 1785-1786.
3．郭应禄，辛钟成主编．男子生殖医学．北京医科大学出版社．2002：159。
4．吴阶平主编．吴阶平泌尿外科学．山东科学技术出版社．2003：993。
5. Poata F, Vecci AM, Graroato AM, et al. P27 expression in normal epithelium benign and neoplastic breast veisons. J Pathol, 2002, 196(1): 26.
6. Loda M, Cukor B, Tam SW, et al. Increased proteasome-dependent degradation of The cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med, 1997, 3(2): 231-234.
7. Yang G, Ayala G, Marzo AD, et al. Elevated skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clinical CancerResearch, 2002, 8(11): 3419-3426.
8. Tsukamoto S, Sugio K, Sakada T, et al. Reduced expression of cell-cycle regulator p27 correlates with a shortened survival in non-small cells lung cancer. Lung Cancer, 2001, 34(1): 83-90.
9. Kuo MY, Hsu HY, Kok SH, et al. Prognostic role of p27 expression in oral squamous cell carcinoma in Taiman. Oroal Oncol, 2002, 38(2): 172.
10. Masuda M, Takano Y, Iki AM, et al. Cyclin-dependent kinase inhibitor P27kipl expression in transitional cell carcinoma of renal pelvis and ureter. Cancer Letters,2000,150(2):183-189.
11. Langner C, Wasielewski R,Ratschek M,et al.Biological significance of p27 and Skp2 expression in renal cell carcinoma.A systemati systematic analysis of primary and metastatic tumor tissues using a tissue microarray technique.Virchows Archiv,2004,445 (6):631- 636.
12. Signoretti S,Di Marcotullio L,Richardson A,et al. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. Clin Invest2002, 110(5): 633-641.
13. Yang G, Ayala G, Marzo AD, et al. Elevated skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clinical Cancer Research, 2002, 8(11):3419-3426.
14. Shirane M,Harumiyal Y,Ishida H,et al.Down-regulation of p27 by two mechanisms Ubiquitin-mediated degradation and proteolytic processing. J Biol chem 1999,274(20): 13886-13893.
15. Renmmele W, Stegner HE.Recommendation for uniform definition of antimmunoreactive score(IRS) for immunohistochemical estrogen receptordection (ER-CIA) in brest cancer tissue.Pathologe 1987, 8(1): 138-140.
16. Pietenpol JA, BohlanderSK, Sato Y, etal. Assignment of the human p27 gene to 12p and its analysis in leukemias. Cancer Res, 1995, 55(6):1206-1210.
17. Ponce Castaneda MV, Lee MH , Latres E, et al. p27 chromosomal mapping to 12p12-12p13. 1 and absence of mutations in human tumors. Cancer Res, 1995, 55(6):1211-1214.
18. 王华,王靖花.p27与肿瘤.中华病理学杂志, 1999, 28(2):140-142.
19. Kawamata N, Morosetti R, Miller CW , et al. Molecular analysis of the cyclin-dependent kinase inhibitor gene p27 in human malignancies. Cancer Res, 1995, 55(11):2266-2269.
20. Lloyd RV, Jin L, Qian X, etal. Aberrant p27 expression in endocrine and other tumors. Am J Pathol, 1997, 150(2):401-407.
21. Esposito V, Baldi A, DeLuca A, etal. Prognostic role of the cyclin- dependent kinase inhibitor p27 in non-small cell lung cancer.Cancer Res, 1997, 57(16):3381-3385.
22. LodaM, CukorB, Tam SW, etal. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive coloretal carcinomas. Nat Med, 1997, 3(2):231-234.
23. Yasui W, Kudo Y, Semba S, et al. Reduced expression of cyclin dependent kinase inhibitor p27 is associated with advanced stage and invasiveness of gastric carcinomas. Jpn J Cancer Res, 1997, 88(7):625-629.
24. Zi X, Adam WG,Hsing JK, et al.A flavonoid antioxidant,silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors,G_1 arrest,and anticarcinogenic effects in human prostate carcinoma DU145 cells.Cancer Res, 1998,58(9): 1920-1923.
25. Zhang JH, Wang XF, Ye HY, et al. Expression of p27 protein and cyclinD1 protein in renal cell carcinomaion. Chin J Urol, 2001,22 (5): 264-266.
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