Top

Published in:

Open Access 01-12-2013 | Research

The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma

Authors: Simone Brandt, Chiara Montagna, Antoin Georgis, Peter J Schüffler, Marco M Bühler, Burkhardt Seifert, Thore Thiesler, Alessandra Curioni-Fontecedro, Ivan Hegyi, Silvia Dehler, Vittoria Martin, Marianne Tinguely, Davide Soldini

Published in: Experimental Hematology & Oncology | Issue 1/2013

Abstract

Background

In diffuse large B-cell lymphomas, gene expression profiling studies attributed a major biologic role to non-neoplastic cells of the tumour microenvironment as its composition and characteristics were shown to predict survival. In particular, the expression of selected genes encoding components of the extracellular matrix was reported to be associated with clinical outcome. Nevertheless, the translation of these data into robust, routinely applicable immunohistochemical markers is still warranted. Therefore, in this study, we analysed the combination of the expression of the extracellular matrix components Fibronectin and SPARC on formalin-fixed paraffin embedded tissue derived from 173 patients with DLBCL in order to recapitulate gene expression profiling data.

Results

The expression of Fibronectin and SPARC was detected in 77/173 (44.5%) and 125/173 (72.3%) cases, respectively, and 55/173 (31.8%) cases were double positive. Patients with lymphomas expressing Fibronectin showed significantly longer overall survival when compared to negative ones (6.3 versus 3.6 years). Moreover, patients with double positive lymphomas also presented with significantly longer overall survival when compared with the remaining cases (11.6 versus 3.6 years) and this combined expression of both markers results in a better association with overall survival data than the expression of SPARC or Fibronectin taken separately (Hazard ratio 0.41, 95% confidence interval 0.17 to 0.95, p = 0.037). Finally, neither Fibronectin nor SPARC expression was associated with any of the collected clinico-pathological parameters.

Conclusions

The combined immunohistochemical assessment of Fibronectin and SPARC, two components of the extracellular matrix, represents an important tool for the prediction of survival in diffuse large B-cell lymphomas. Our study suggests that translation of gene expression profiling data on tumour microenvironment into routinely applicable immunohistochemical markers is a useful approach for a further characterization of this heterogeneous type of lymphoma.

Available only for authorised users

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2008.

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403: 503–511. 10.1038/35000501PubMedCrossRef

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Montserrat E, Lopez-Guillermo A, et al.: The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002, 346: 1937–1947. 10.1056/NEJMoa012914PubMedCrossRef

Harada S, Suzuki R, Uehira K, Yatabe Y, Kagami Y, Ogura M, Suzuki H, Oyama A, Kodera Y, Ueda R, Morishima Y, Nakamura S, Seto M: Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes. Leukemia 1999, 13: 1441–1447. 10.1038/sj.leu.2401487PubMedCrossRef

Yamaguchi M, Seto M, Okamoto M, Ichinohasama R, Nakamura N, Yoshino T, Suzumiya J, Murase T, Miura I, Akasaka T, Tamaru J, Suzuki R, Kagami Y, Hirano M, Morishima Y, Ueda R, Shiku H, Nakamura S: De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood 2002, 99: 815–821. 10.1182/blood.V99.3.815PubMedCrossRef

Suguro M, Tagawa H, Kagami Y, Okamoto M, Ohshima K, Shiku H, Morishima Y, Nakamura S, Seto M: Expression profiling analysis of the CD5+ diffuse large B-cell lymphoma subgroup: development of a CD5 signature. Cancer Sci 2006, 97: 868–874. 10.1111/j.1349-7006.2006.00267.xPubMedCrossRef

Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, et al.: Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008, 359: 2313–2323. 10.1056/NEJMoa0802885PubMedCrossRef

Singh P, Carraher C, Schwarzbauer JE: Assembly of fibronectin extracellular matrix. Annu Rev Cell Dev Biol 2010, 26: 397–419. 10.1146/annurev-cellbio-100109-104020PubMedCentralPubMedCrossRef

Fabris M, Quartuccio L, Salvin S, Pozzato G, De Re V, Mazzaro C, Ferri C, Baldini C, De Vita S: Fibronectin gene polymorphisms are associated with the development of B-cell lymphoma in type II mixed cryoglobulinemia. Ann Rheum Dis 2008, 67: 80–83. 10.1136/ard.2006.067637PubMedCrossRef

10.

Chlenski A, Cohn SL: Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol 2010, 21: 55–65. 10.1016/j.semcdb.2009.11.018PubMedCrossRef

11.

Meyer PN, Fu K, Greiner T, Smith L, Delabie J, Gascoyne R, Ott G, Rosenwald A, Braziel R, Campo E, Vose J, Lenz G, Staudt L, Chan W, Weisenburger DD: The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol 2011, 135: 54–61. 10.1309/AJCPJX4BJV9NLQHYPubMedCrossRef

12.

Perry AM, Cardesa-Salzmann TM, Meyer PN, Colomo L, Smith LM, Fu K, Greiner TC, Delabie J, Gascoyne RD, Rimsza L, Jaffe ES, Ott G, Rosenwald A, Braziel RM, Tubbs R, Cook JR, Staudt LM, Connors JM, Sehn LH, Vose JM, Lopez-Guillermo A, Campo E, Chan WC, Weisenburger DD: A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma. Blood 2012, 120: 2290–2296. 10.1182/blood-2012-05-430389PubMedCentralPubMedCrossRef

13.

Kaspar M, Zardi L, Neri D: Fibronectin as target for tumor therapy. Int J Cancer 2006, 118: 1331–1339. 10.1002/ijc.21677PubMedCrossRef

14.

Johannsen M, Spitaleri G, Curigliano G, Roigas J, Weikert S, Kempkensteffen C, Roemer A, Kloeters C, Rogalla P, Pecher G, Miller K, Berndt A, Kosmehl H, Trachsel E, Kaspar M, Lovato V, Gonzalez-Iglesias R, Giovannoni L, Menssen HD, Neri D, de Braud F: The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma. Eur J Cancer 2010, 46: 2926–2935. 10.1016/j.ejca.2010.07.033PubMedCrossRef

15.

Soldini D, Montagna C, Schuffler P, Martin V, Georgis A, Thiesler T, Curioni-Fontecedro A, Went P, Bosshard G, Dehler S, Mazzuchelli L, Tinguely M: A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome. Ann Oncol 2013, 24: 193–201. 10.1093/annonc/mds209PubMedCrossRef

16.

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004, 103: 275–282. 10.1182/blood-2003-05-1545PubMedCrossRef

Title: The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma
Authors: Simone Brandt
Chiara Montagna
Antoin Georgis
Peter J Schüffler
Marco M Bühler
Burkhardt Seifert
Thore Thiesler
Alessandra Curioni-Fontecedro
Ivan Hegyi
Silvia Dehler
Vittoria Martin
Marianne Tinguely
Davide Soldini
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Experimental Hematology & Oncology / Issue 1/2013
Electronic ISSN: 2162-3619
DOI: https://doi.org/10.1186/2162-3619-2-27

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Bone marrow non-mesenchymal mononuclear cells induce functional differentiation of neuroblastoma cells

Vincristine could partly suppress stromal support to T-ALL blasts during pegylated arginase I treatment

Evaluation of serum Amphiregulin levels in breast cancer patients and cancer-free controls

In vitro and in vivo properties of CD133 expressing cells from human lung cancer cell lines

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison

Keynote webinar | Spotlight on antibody–drug conjugates in cancer