Skip to main content
Top
Published in: Virchows Archiv 4/2007

01-04-2007 | Original Article

Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms

Authors: E. Compérat, P. Camparo, R. Haus, E. Chartier-Kastler, B. Radenen, F. Richard, F. Capron, V. Paradis

Published in: Virchows Archiv | Issue 4/2007

Login to get access

Abstract

Aurora-A, a member of serine/threonine kinase, is implied in mitosis and centrosome maturation. Increasing levels of Aurora-A have been shown to be present in several malignancies and especially in bladder cancer. No immunohistochemical marker has shown to be able to predict the clinical outcome of patients with superficial bladder cancer, except MIB-1, as a predictive marker of relapse and progression. The aim was to investigate the expression of Aurora-A and MIB-1 in tissue micro arrays of superficial bladder cancer representative of pTa papillary urothelial neoplasm with different degrees of aggressiveness (low malignant potential [PUNLMP], non-invasive papillary urothelial carcinoma low grade [NILGC], non-invasive papillary urothelial carcinoma high grade [NIHGC] and carcinoma in situ). We analysed predictive values of both markers, their specificity and sensitivity in tumor recurrence. Aurora-A was a sensitive marker to predict tumor recurrence especially for pTa (PUNLMP, NILGC; PUNLMP p < 0.001, NILGC p < 0.001) with statistical significant correlation between immunohistochemical staining and clinical outcome. MIB-1 expression displayed statistical difference p = 0.002 in the PUNLMP group and p = 0.03 in the NILGC group. Aurora-A is a more sensitive marker than MIB-1 to predict relapse in pTa bladder neoplasias. The combination of both markers seems to have a very powerful predictive value of recurrence (p < 0.001).
Literature
1.
go back to reference Alsheikh A, Mohamedali Z, Jones E, Masterson J, Gilks CB (2001) Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/International Society of Urologic Pathology. Mod Pathol 14(4):267–272PubMedCrossRef Alsheikh A, Mohamedali Z, Jones E, Masterson J, Gilks CB (2001) Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/International Society of Urologic Pathology. Mod Pathol 14(4):267–272PubMedCrossRef
2.
go back to reference Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD et al (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392(6673):300–303PubMedCrossRef Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD et al (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392(6673):300–303PubMedCrossRef
4.
go back to reference Ducat D, Zheng Y (2004) Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res 301(1):60–67PubMedCrossRef Ducat D, Zheng Y (2004) Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res 301(1):60–67PubMedCrossRef
5.
go back to reference Duchrow M, Schluter C, Wohlenberg C, Flad HD, Gerdes J (1996) Molecular characterization of the gene locus of the human cell proliferation-associated nuclear protein defined by monoclonal antibody Ki-67. Cell Prolif 29(1):1–12PubMedCrossRef Duchrow M, Schluter C, Wohlenberg C, Flad HD, Gerdes J (1996) Molecular characterization of the gene locus of the human cell proliferation-associated nuclear protein defined by monoclonal antibody Ki-67. Cell Prolif 29(1):1–12PubMedCrossRef
6.
go back to reference Dybowski B, Kupryjanczyk J, Rembiszewska A, Pykalo R, Borkowski A (2003) P27(Kip1) and Ki-67 expression analysis in transitional cell carcinoma of the bladder. Urol Res 31(6):397–401PubMedCrossRef Dybowski B, Kupryjanczyk J, Rembiszewska A, Pykalo R, Borkowski A (2003) P27(Kip1) and Ki-67 expression analysis in transitional cell carcinoma of the bladder. Urol Res 31(6):397–401PubMedCrossRef
7.
go back to reference Dyrskjot L, Zieger K, Kruhoffer M, Thykjaer T, Jensen JL, Primdahl H et al (2005) A molecular signature in superficial bladder carcinoma predicts clinical outcome. Clin Cancer Res 11(11):4029–4036PubMedCrossRef Dyrskjot L, Zieger K, Kruhoffer M, Thykjaer T, Jensen JL, Primdahl H et al (2005) A molecular signature in superficial bladder carcinoma predicts clinical outcome. Clin Cancer Res 11(11):4029–4036PubMedCrossRef
8.
go back to reference Eble JN, Sauter G, Epstein JI, Sesterhenn IA (2004) Tumours of the urinary system and male genital organs. IARC, Lyon, France Eble JN, Sauter G, Epstein JI, Sesterhenn IA (2004) Tumours of the urinary system and male genital organs. IARC, Lyon, France
9.
go back to reference Fraizer GC, Diaz MF, Lee IL, Grossman HB, Sen S (2004) Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. Int J Oncol 25(6):1631–1639PubMed Fraizer GC, Diaz MF, Lee IL, Grossman HB, Sen S (2004) Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. Int J Oncol 25(6):1631–1639PubMed
10.
go back to reference Frank I, Cheville JC, Blute ML, Lohse CM, Karnes RJ, Weaver AL et al (2004) Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement. Cancer 101(8):1803–1808PubMedCrossRef Frank I, Cheville JC, Blute ML, Lohse CM, Karnes RJ, Weaver AL et al (2004) Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement. Cancer 101(8):1803–1808PubMedCrossRef
11.
go back to reference Gattegno B, Chopin D (2001) Natural history of superficial bladder tumors. Prog Urol 11(5):963–990PubMed Gattegno B, Chopin D (2001) Natural history of superficial bladder tumors. Prog Urol 11(5):963–990PubMed
12.
go back to reference Gritsko TM, Coppola D, Paciga JE, Yang L, Sun M, Shelley SA et al (2003) Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res 9(4):1420–1426PubMed Gritsko TM, Coppola D, Paciga JE, Yang L, Sun M, Shelley SA et al (2003) Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res 9(4):1420–1426PubMed
13.
14.
go back to reference Helpap B, Schmitz-Drager BJ, Hamilton PW, Muzzonigro G, Galosi AB, Kurth KH et al (2003) Molecular pathology of non-invasive urothelial carcinomas (part I). Virchows Arch 442(4):309–316PubMed Helpap B, Schmitz-Drager BJ, Hamilton PW, Muzzonigro G, Galosi AB, Kurth KH et al (2003) Molecular pathology of non-invasive urothelial carcinomas (part I). Virchows Arch 442(4):309–316PubMed
15.
go back to reference Holmang S, Andius P, Hedelin H, Wester K, Busch C, Johansson SL (2001) Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol 165(4):1124–1128, discussion 1128–1130PubMedCrossRef Holmang S, Andius P, Hedelin H, Wester K, Busch C, Johansson SL (2001) Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol 165(4):1124–1128, discussion 1128–1130PubMedCrossRef
16.
go back to reference Holmang S, Johansson SL (2002) Stage Ta-T1 bladder cancer: the relationship between findings at first follow-up cystoscopy and subsequent recurrence and progression. J Urol 167(4):1634–1637PubMedCrossRef Holmang S, Johansson SL (2002) Stage Ta-T1 bladder cancer: the relationship between findings at first follow-up cystoscopy and subsequent recurrence and progression. J Urol 167(4):1634–1637PubMedCrossRef
17.
go back to reference Jeng YM, Peng SY, Lin CY, Hsu HC (2004) Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res 10(6):2065–2071PubMedCrossRef Jeng YM, Peng SY, Lin CY, Hsu HC (2004) Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res 10(6):2065–2071PubMedCrossRef
18.
go back to reference Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S et al (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443(2):115–121PubMedCrossRef Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S et al (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443(2):115–121PubMedCrossRef
19.
go back to reference Kamada K, Yamada Y, Hirao T, Fujimoto H, Takahama Y, Ueno M et al (2004) Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep 12(3):593–599PubMed Kamada K, Yamada Y, Hirao T, Fujimoto H, Takahama Y, Ueno M et al (2004) Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep 12(3):593–599PubMed
20.
go back to reference Knowles MA (2001) What we could do now: molecular pathology of bladder cancer. Mol Pathol 54(4):215–221PubMedCrossRef Knowles MA (2001) What we could do now: molecular pathology of bladder cancer. Mol Pathol 54(4):215–221PubMedCrossRef
21.
go back to reference Lebret T, Bohin D, Kassardjian Z, Herve JM, Molinie V, Barre P et al (2000) Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette–Guerin instillations. J Urol 163(1):63–67PubMedCrossRef Lebret T, Bohin D, Kassardjian Z, Herve JM, Molinie V, Barre P et al (2000) Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette–Guerin instillations. J Urol 163(1):63–67PubMedCrossRef
22.
go back to reference Li D, Zhu J, Firozi PF, Abbruzzese JL, Evans DB, Cleary K et al (2003) Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9(3):991–997PubMed Li D, Zhu J, Firozi PF, Abbruzzese JL, Evans DB, Cleary K et al (2003) Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9(3):991–997PubMed
23.
go back to reference Mai KT, Elmontaser G, Perkins DG, Yazdi HM, Stinson WA, Thijssen A (2004) Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma. BJU Int 94(4):544–547PubMedCrossRef Mai KT, Elmontaser G, Perkins DG, Yazdi HM, Stinson WA, Thijssen A (2004) Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma. BJU Int 94(4):544–547PubMedCrossRef
24.
go back to reference Nocito A, Bubendorf L, Maria Tinner E, Suess K, Wagner U, Forster T et al (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194(3):349–357PubMedCrossRef Nocito A, Bubendorf L, Maria Tinner E, Suess K, Wagner U, Forster T et al (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194(3):349–357PubMedCrossRef
25.
go back to reference Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443(2):122–132PubMedCrossRef Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443(2):122–132PubMedCrossRef
26.
go back to reference Richter J, Jiang F, Gorog JP, Sartorius G, Egenter C, Gasser TC et al (1997) Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. Cancer Res 57(14):2860–2864PubMed Richter J, Jiang F, Gorog JP, Sartorius G, Egenter C, Gasser TC et al (1997) Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. Cancer Res 57(14):2860–2864PubMed
27.
go back to reference Sanchez-Carbayo M (2004) Recent advances in bladder cancer diagnostics. Clin Biochem 37(7):562–571PubMedCrossRef Sanchez-Carbayo M (2004) Recent advances in bladder cancer diagnostics. Clin Biochem 37(7):562–571PubMedCrossRef
28.
go back to reference Sen S, Zhou H, Zhang RD, Yoon DS, Vakar-Lopez F, Ito S et al (2002) Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94(17):1320–1329PubMed Sen S, Zhou H, Zhang RD, Yoon DS, Vakar-Lopez F, Ito S et al (2002) Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94(17):1320–1329PubMed
29.
go back to reference Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP (2003) Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 61(6):1140–1145PubMedCrossRef Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP (2003) Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 61(6):1140–1145PubMedCrossRef
30.
go back to reference Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718PubMedCrossRef Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718PubMedCrossRef
Metadata
Title
Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms
Authors
E. Compérat
P. Camparo
R. Haus
E. Chartier-Kastler
B. Radenen
F. Richard
F. Capron
V. Paradis
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2007
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-007-0383-x

Other articles of this Issue 4/2007

Virchows Archiv 4/2007 Go to the issue