Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer

详细信息    查看全文

• 作者：Marina Fran?a de Resende (1)
  Samantha Vieira (1)
  Ludmilla Thomé Domingos Chinen (1)
  Francesco Chiappelli (2)
  Francisco Paulo da Fonseca (1)
  Gustavo Cardoso Guimar?es (3)
  Fernando Augusto Soares (1)
  Ivan Neves (1)
  Simone Pagotty (1)
  Peter A Pellionisz (2)
  Andre Barkhordarian (2)
  Xenia Brant (1)
  Rafael Malagoli Rocha (1) (4)
  
• 关键词：FISH ; Immunohistochemistry ; Prostate cancer ; TOP2A
• 刊名：Journal of Translational Medicine
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：11
• 期：1
• 全文大小：1920KB
• 参考文献：1. Tsavaris N, Lazaris A, Kosmas C, Gouveris P, Kavantzas N, Kopterides P, Papathomas T, Agrogiannis G, Zorzos H, Kyriakou V, Patsouris E: Topoisomerase I and IIα protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy. / Cancer Chemother Pharmacol 2009, 64:391-98. CrossRef
  2. Mirski SE, Bielawski JC, Cole SP: Identification of functional nuclear export sequences in human topoisomerase IIα and β. / Biochem Biophys Res Commun 2003, 306:905-11. CrossRef
  3. Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. / CA Cancer J Clin 2010, 60:277-00. CrossRef
  4. Malhotra S, Lapointe J, Salari K, Higgins JP, Ferrari M, Montgomery K, van de Rijn M, Brooks JD, Pollack JR: A Tri-Marker Proliferation Index Predicts Biochemical Recurrence after Surgery for Prostate Cancer. / PLoS One 2011, 6:e20293. CrossRef
  5. Willman JH, Holden JA: Immunohistochemical Staining for DNA Topoisomerase II-Alpha in Benign, Premalignant Lesions of the Prostate. / Prostate 2000, 42:280-86. CrossRef
  6. Hughes C, Murphy A, Martin C, Fox E, Ring M, Sheils O, Loftus B, O'Leary J: Topoisomerase II-α expression increases with increasing Gleason score and with hormone insensitivity in prostate carcinoma. / J Clin Pathol 2006, 59:721-24. CrossRef
  7. Sullivan GF, Amenta PS, Villanueva JD, Alvarez CJ, Yang JM, Hait WN: The Expression of Drug Resistance Gene Products during the Progression of Human Prostate Cancer. / Clin Cancer Res 1998, 4:1393-403.
  8. Hasby EA, Saied EM: Immunohistochemical Expression of Topoisomerase II Alpha and Her-2/neu in Prostatic Carcinoma and Benign Prostatic Hyperplasia. / J Egypt Natl Canc Inst 2008, 20:158-67.
  9. Murphy AJ, Hughes CA, Barrett C, Magee H, Loftus B, O'Leary JJ, Sheils O: Low-Level TOP2A Amplification in Prostate Cancer Is Associated with HER2 Duplication, Androgen Resistance, and Decreased Survival. / Cancer Res 2007, 67:2893-898. CrossRef
  10. Karnes RJ, Cheville JC, Ida CM, Sebo TJ, Nair AA, Tang H, Munz JM, Kosari F, Vasmatzis G: The ability of biomarkers to predict systemic progression in men with high-risk prostate cancer treated surgically is dependent on ERG status. / Cancer Res 2010, 70:8994-002. CrossRef
  11. Ida CM, Cheville JC, Karnes R: Topoisomerase IIα Protein Expression Is Predictive of Outcome in Gleason Score?≥- Prostate Cancer Patients Treated Surgically and Is Dependent on ERG Status. / Mod Pathol 2010, 23:422A. CrossRef
  12. Nakopoulou L, Zervas A, Lazaris AC, Constantinides C, Stravodimos C, Davaris P, Dimopoulos C: Predictive value of topoisomerase IIα immunostaining in urothelial bladder carcinoma. / J Clin Pathol 2001, 54:309-13. CrossRef
  13. Albadine R, Wang W, Brownlee NA, Toubaji A, Billis A, Argani P, Epstein JI, Garvin AJ, Cousi R, Schaeffer EM, Pavlovich C, Netto GJ: Topoisomerase II α status in renal medullary carcinoma: immuno-expression and gene copy alterations of a potential target therapy. / J Urol 2009, 182:735-40. CrossRef
  14. Schindlbeck C, Mayr D, Olivier C, Rack B, Engelstaedter V, Jueckstock J, Jenderek C, Andergassen U, Jeschke U, Friese K: Topoisomerase IIα expression rather than gene amplification predicts responsiveness of adjuvant anthracycline-based chemotherapy in women with primary breast cancer. / J Cancer Res Clin Oncol 2010, 136:1029-037. CrossRef
  15. Shvero J, Koren R, Shvili I, Yaniv E, Sadov R, Hadar T: Expression of Human DNA topoisomerase ii-α in squamous cell carcinoma of the larynx and its correlation with clinicopathologic variables. / Am J Clin Pathol 2008, 130:934-39. CrossRef
  16. Shamaa AA, Zyada MM, Wagner M, Awad SS, Osman MM, Abdel Azeem AA: The significance of Epstein Barr Virus (EBV) & DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC). / Diagn Pathol 2008, 3:45. CrossRef
  17. Faggad A, Darb-Esfahani S, Wirtz R, Sinn B, Sehouli J, K?nsgen D, Lage H, Weichert W, Noske A, Budczies J, Müller BM, Buckendahl AC, R?ske A, Eldin Elwali N, Dietel M, Denkert C: Topoisomerase IIα mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. / Mod Pathol 2009, 22:579-88. CrossRef
  18. Gotlieb WH, Goldberg I, Weisz B, Davidson B, Novikov I, Kopolovic J, Ben-Baruch G: Topoisomerase II Immunostaining as a Prognostic Marker for Survival in Ovarian Cancer. / Gynecol Oncol 2001, 82:99-04. CrossRef
  19. O'Connor JK, Hazard LJ, Avent JM, Lee RJ, Fischbach J, Gaffney DK: Topoisomerase II alpha expression correlates with diminished disease-free survival in invasive breast cancer. / Int J Radiat Oncol Biol Phys 2006, 65:1411-415. CrossRef
  20. da Cunha IW, De Brot L, Carvalho KC, Rocha RM, Fregnani JH, Falzoni R, Ferreira Fde O, Aguiar S Jr, Lopes A, Muto NH, Reis LF, Soares FA, Vassallo J: Prognostication of Soft Tissue Sarcomas Based on Chromosome 17q Gene and Protein Status: Evaluation of TOP2A, HER-2/neu, and Survivin. / Ann Surg Oncol 2011, 19:1790-799. CrossRef
  21. Durbecq V, Desmed C, Paesmans M, Cardoso F, Di Leo A, Mano M, Rouas G, Leroy JY, Sotiriou C, Piccart M, Larsimont D: Correlation between topoisomerase-IIalpha gene amplification and protein expression in HER-2 amplified breast cancer. / Int J Oncol 2004, 25:1473-479.
  22. Mueller RE, Parkes RK, Andrulis I, O'Malley FP: Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples. / Genes Chromosomes Cancer 2004, 39:288-97. CrossRef
  23. Kanta SY, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A: Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. / Hum Pathol 2006, 37:1333-343. CrossRef
  24. Kim EJ, Lee YS, Kim YJ, Kim MJ, Ha YS, Jeong P, Lee OJ, Kim WJ: Clinical Implications and Prognostic Values of Topoisomerase-II Alpha Expression in Primary Non-muscle-invasive Bladder Cancer. / Urology 2010, 75:1516.e9-3.
  25. Bredel M, Piribauer M, Marosi C, Birner P, Gatterbauer B, Fischer I, Str?bel T, R?ssler K, Budka H, Hainfellner JA: High expression of DNA topoisomerase IIα and Ki-67 antigen is associated with prolonged survival in glioblastoma patients. / Eur J Cancer 2002, 38:1343-347. CrossRef
  26. Yan S, Shun-Chang J, Li C, Jie L, Ya-Li L, Ling-Xiong W: Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer. / BMC Cancer 2010, 10:621. CrossRef
  27. Alenda O, Ploussard G, Mouracade P, Xylinas E, de la Taille A, Allory Y, Vordos D, Hoznek A, Abbou CC, Salomon L: Impact of the primary Gleason pattern on biochemical recurrence-free survival after radical prostatectomy: a single-center cohort of 1,248 patients with Gleason 7 tumors. / World J Urol 2011, 29:671-76. CrossRef
  28. Di Leo A, Isola J: Topoisomerase IIα as a Marker Predicting the Efficacy of Anthracyclines in Breast Cancer: Are We at the End of the Beginning? / Clin Breast Cancer 2003, 4:179-86.
  29. Spitaleri G, Matei DV, Curigliano G, Detti S, Verweij F, Zambito S, Scardino E, Rocco B, Nolè F, Ariu L, De Pas T, de Braud F, De Cobelli O: Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer. / Ann Oncol 2009, 20:498-02. CrossRef
  30. Vaishampayan U, Fontana J, Du W, Hussain M: Phase II trial of estramustine and etoposide in androgen-sensitive metastatic prostate carcinoma. / Am J Clin Oncol 2004, 27:550-54. CrossRef
  31. Fizazi K, Beuzeboc P, Lumbroso J, Haddad V, Massard C, Gross-Goupil M, Di Palma M, Escudier B, Theodore C, Loriot Y, Tournay E, Bouzy J, Laplanche A: Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. / J Clin Oncol 2009, 27:2429-435. CrossRef
  
• 作者单位：Marina Fran?a de Resende (1)
  Samantha Vieira (1)
  Ludmilla Thomé Domingos Chinen (1)
  Francesco Chiappelli (2)
  Francisco Paulo da Fonseca (1)
  Gustavo Cardoso Guimar?es (3)
  Fernando Augusto Soares (1)
  Ivan Neves (1)
  Simone Pagotty (1)
  Peter A Pellionisz (2)
  Andre Barkhordarian (2)
  Xenia Brant (1)
  Rafael Malagoli Rocha (1) (4)
  
  1. Department of Pathology, A. C. Camargo Cancer Hospital, Sao Paulo, Brazil
  2. UCLA School of Dentistry, Los Angeles, CA, USA
  3. Department of Urology, A. C. Camargo Cancer Hospital, Sao Paulo, Brazil
  4. Rua Professor Ant?nio Prudente 211, Liberdade S?o Paulo, SP, 01509-900, Brazil
  

文摘

Background TOP2A encodes for topoisomerase IIα, a nuclear enzyme that controls DNA topological structure and cell cycle progression. This enzyme is a marker of cell proliferation in normal and neoplastic tissues; however, little information is available about its expression in prostate cancer (PCa). Methods Immunohistochemistry (IHC) was automated using mouse monoclonal antibody against TOP2A (clone SWT3D1; DAKO, Carpenteria, CA, USA) at dilution 1:800 and Flex Plus detection system in autostainer 48Ultra (DAKO). FISH was performed using TOP2A (17q21)/ CEP17 probe kit (Kreateck Biotechnology, San Diego, CA, USA). Biochemical and pathological data from 193 patients with PCa were retrieved for the analysis, whose significance was considered when p-lt;-.05. Also, fractal analysis was performed in a subset of 20 randomly selected cases. Results TOP2A protein expression correlated with higher Gleason scores and higher levels of preoperative PSA (p--.018 and p--.011). Patients with higher levels of TOP2A presented shorter biochemical recurrence-free survival (BRFS) (p--.001). In multivariate analysis, we found that TOP2A remained an independent prognostic factor of BRFS, with a relative risk of 1.98 (p--.001; 95% CI, 1.338-.93); thus, cases that expressed high levels of this enzyme had a shorter BRFS compared with TOP2A-negative or TOP2A-low cases. No alterations in TOP2A gene status nor correlation between FISH and IHC results were observed. Concerning fractal analysis, patients who expressed higher levels of TOP2A have angiolymphatic invasion and presented higher Gleason scores (p--.033 and p--.025, respectively). Also, patients with higher expression of TOP2A presented shorter BRFS (p--.001). Conclusions This is the first study to perform TOP2A protein and gene digital assessment and fractal analysis in association with BRFS in a large series of PCa. Also, we show that TOP2A gene copy number alterations are not observed in this type of tumor. So, higher protein expression of TOP2A is not related to gene amplification in PCa. Furthermore, TOP2A protein assessment has prognostic importance and, due to its relation with poor outcome, TOP2A IHC evaluation in the biopsy can represent an important tool for selecting the most suitable surgical and clinical approach for patients with PCa.