Topo IIα gene alterations correlated with survival in patients with diffuse large B-cell lymphoma
Zhenwen Chen
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorJinfen Wang
Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorHongwei Zhang
Department of Hematology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorDongmei Liu
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorYi Li
Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorYirong Xu
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorDongfeng Tan
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Search for more papers by this authorDong Chen
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorXia Zhao
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorGuoping Wang
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZhenwen Chen
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorJinfen Wang
Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorHongwei Zhang
Department of Hematology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorDongmei Liu
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorYi Li
Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
Search for more papers by this authorYirong Xu
Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
Search for more papers by this authorDongfeng Tan
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Search for more papers by this authorDong Chen
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorXia Zhao
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorGuoping Wang
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorAbstract
Eur J Clin Invest 2012; 42 (3): 310–320
Background Topoisomerase IIα (topo IIα) protein expression has prognostic significance in many cancers. However, it is still unclear whether topo IIα protein expression and gene alterations play roles as prognostic factors in diffuse large B-cell lymphoma (DLBCL).
Materials and methods We selected 102 patients with DLBCL who were homogeneously treated with CHOP chemotherapy and followed up. Using tissue microarray technology, all of the cases, consisting of 25 germinal centre B-cell-like (GCB) and 77 nongerminal centre B-cell-like (non-GCB) types, were studied. Topo IIα protein expression was detected by immunohistochemistry. Gene copy number of topo IIα was analysed by chromogenic in situ hybridization. Cox regression, chi-square test and Kaplan–Meier statistics were performed using SPSS 15·0.
Results Topo IIα protein overexpression was found in 91 (91/102, 89·2%) cases, while topo IIα gene amplification was absent in all cases. Chromosome 17 deletion was identified in 3 (3/102, 2·9%) cases, diploid in 66 (66/102, 64·7%) cases and aneuploidy in 33 (33/102, 32·4%) cases. By multivariate analysis, no significant differences in progression-free survival (PFS) and overall survival (OS) were observed in patients with topo IIα protein overexpression (P > 0·05), while chromosome 17 aneuploidy predicted worse PFS and OS (P < 0·001).
Conclusions These results suggested that chromosome 17 aneuploidy, but not topo IIα protein expression, could predict worse survival in patients with DLBCL.
References
- 1 Chan WC, Armitage JO, Gascoyne R, Harris NL. The non-Hodgkin’s lymphoma classification project: a clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood 1997; 89: 3909–18.
- 2 Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503–11.
- 3 Rosenwald A, Wright G, Chan WC, Campo E, Fisher R, Gascoyne R et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. New Engl J Med 2002; 346: 1937–47.
- 4 Hans CP, Weisenberger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2003; 103: 275–82.
- 5 Coiffier B. Diffuse large cell lymphoma. Curr Opin Oncol 2001; 13: 325–34.
- 6 Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RSK, Kuppers R et al. Hypermutation of multiple protooncogenes in B-cell diffuse large-cell lymphomas. Nature 2001; 412: 341–6.
- 7 Lossos IS, Czerwinski DK, Alizadeh AA, Wechser MA, Tibshirani R, Botstein D et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. New Engl J Med 2004; 350: 1828–37.
- 8 Linderoth J, Jerkeman M, Cavallin SE, Kvaloy S, Torlakovic E. Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lymphoma: a nordic lymphoma group study. Clin Cancer Res 2003; 9: 722–8.
- 9 Goswami PC, Roti JL, Hunt CR. The cell cycle-coupled expression of topoisomerase II α during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation. Mol Cell Biol 1996; 16: 1500–8.
- 10 Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP. Structural organization of the human TOP2A and TOP2B gene. Gene 1998; 221: 255–66.
- 11 Guerin E, Entz-Werle N, Eyer D, Pencreach E, Schneider A, Falkenrodt AP et al. Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia. Leukemia 2003; 17: 532–40.
- 12 Bhargava R, Lal P, Chen B. HER-2/neu and topoisomerase IIa gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol 2005; 123: 889–95.
- 13 Schrader C, Meusers P, Brittinger G, Teymoortash A, Siebmann JU, Janssen D et al. Topoisomerase IIalpha expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome. Leukemia 2004; 18: 1200–6.
- 14 Korkolopoulou P, Vassilakopoulos TP. Topoisomerase IIa as a prognostic factor in mantle cell lymphoma. Leukemia 2004; 18: 1347–9.
- 15 Doussis-Anagnostopoulou IA, Vassilakopoulos TP, Thymara I, Korkolopoulou P, Angelopoulou MK, Siakantaris MP et al. Topoisomerase IIa expression as an independent prognostic factor in Hodgkin’s lymphoma. Clin Cancer Res 2008; 14: 1759–66.
- 16 Jinfen W, Lillian Y, William W, Clive RT. Distribution and ZAP-70 expression of WHO lymphoma categories in Shanxi, China: a review of 447 cases using a tissue microarray technique. Appl mmunohistochem Mol Morphol 2005; 13: 323–32.
- 17 Holden JA, Perkins SL, Snow GW, Kjeldsberg CR. Immunohistochemical staining for DNA topoisomerase II in non-Hodgkin’s lymphomas. Am J Clin Pathol 1995; 104: 54–9.
- 18 Korkolopoulou P, Angelopoulou M, Siakantari M, Mitropoulos F, Vassilakopoulos T, Zorzos H et al. Evaluation of DNA topoisomerase IIa expression provides independent prognostic information in non-Hodgkin’s lymphomas. Histopathology 2001; 38: 45–53.
- 19 Pentheroudakis G, Goussia A, Voulgaris E, Nikolaidis K, Ioannidou E, Papoudou-Bai A et al. High levels of topoisomerase IIa protein expression in diffuse large B-cell lymphoma are associated with high proliferation, germinal center immunophenotype, and response to treatment. Leuk Lymphoma 2010; 51: 1260–8.
- 20 Dingemans AMC, Ark-Otte J, Spana S, Scagliottid GV, Valk PVD, Postmusb PE et al. Topoisomerase IIa and other drug resistance markers in advanced non-small cell lung cancer. Lung Cancer 2001; 32: 117–28.
- 21 Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S et al. Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res 2002; 8: 1061–7.
- 22 Leo AD, Gancberg D, Larsimont D, Tanner M, Jarvinen T, Rouas G et al. HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 2002; 8: 1107–16.
- 23 Deffie AM, McPherson JP, Gupta RS, Hedley DW, Goldenberg GJ. Multifactorial resistance to antineoplastic agents in drug- resistant P388 murine leukemia, Chinese hamster ovary, and human HeLa cells, with emphasis on the role of DNA topoisomeraseII. Biochem Cell Biol 1992; 70: 354–64.
- 24 Friche E, Danks MK, Schmidt CA, Beck WT. Decreased DNA topoisomerase II in daunorubicin-resistant Ehrlich ascites tumor cells. Cancer Res 1991; 51: 4213–8.
- 25 Provencio M, Corbacho C, Salas C, Millan I, Espana P, Bonilla F et al. The topoisomerase IIA expression correlates with survival in patients with advanced Hodgkin’s lymphoma. Clin Cancer Res 2003; 9: 1406–11.
- 26 Bouchalova K, Trojanes R, Kolar Z, Cwiertka K, Cernakova I, Mihal V et al. Analysis of ERBB2 and TOP2A gene status using fluorescence in situ hybridization versus immunohistochemistry in localized breast cancer. Neoplasma 2006; 53: 393–401.
- 27 Monti S, Savage KJ, Kutok JL, Feuerhake F, Kurtin P, Mihm M et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005; 105: 1851–61.
- 28 Feuerhake F, Kutok JL, Monti S, Chen W, LaCasce AS, Cattoretti G et al. NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood 2005; 106: 1392–9.
- 29 Haarer CF, Roberts RA, Frutiger YM, Grogan TM, Rimsza LM. Immunohistochemical classification of de novo, transformed, and relapsed diffuse large B-cell lymphoma into germinal center B-cell and nongerminal center B-cell subtypes correlates with gene expression profile and patient survival. Arch Pathol Lab Med 2006; 130: 1819–24.
- 30 Cortes F, Pastor N, Mateos S, Dominguez I. Roles of DNA topoisomerases in chromosome segregation and mitosis. Mutat Res 2003; 543: 59–66.
- 31 Attia SM, Schmid TE, Badary OA, Hamada FM, Adler ID. Molecular cytogenetic analysis in mouse sperm of chemically induced aneuploidy: studies with topoisomerase II inhibitors. Mutat Res 2002; 520: 1–13.
- 32 Kallio M, Lahdetie J. Effects of DNA topoisomerase inhibitor merbarone in male mouse meiotic divisions in vivo: cell cycle arrest and induction of aneuploidy. Environ Mol Mutagen 1997; 29: 16–27.
- 33 Doak SH. Aneuploidy in upper gastro-intestinal tract cancers-A potential prognostic marker? Mutat Res 2008; 651: 93–104.
- 34 Stoecklein NH, Luebke AM, Erbersdobler A, Knoefel WT, Schraut W, Verde PE et al. Copy number of chromosome 17 but not HER2 amplification predicts clinical outcome of patients with pancreatic ductal adenocarcinoma. J Clin Oncol 2004; 22: 4737–45.
- 35 Simonetti S, Russo R, Ciancia G, Altieri V, Rosa GD, Insabato L. Role of polysomy 17 in transitional cell carcinoma of the bladder: immunohistochemical study of HER2/neu expression and fish analysis of c-erbB-2 gene and chromosome 17. Int J Surg Pathol 2009; 17: 198–205.
