ORIGINAL ARTICLE

Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases

A Tzankov¹, A-C Pehrs², A Zimpfer², S Ascani³, A Lugli², S Pileri³ and S Dirnhofer²

¹ Institute of Pathology, University of Innsbruck, A-6020 Innsbruck, Austria
² Institute of Pathology, University of Basel, CH-4031 Basel, Switzerland
³ Institute of Hematology and Clinical Oncology "L. & A. Seràgnoli", University of Bologna, I-40138 Bologna, Italy

Correspondence to:
Correspondence to:
Dr S Dirnhofer, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland;
sdirnhofer{at}uhbs.ch

Background: Gene expression profiling of diffuse large B cell lymphoma (DLBCL) revealed three disease types: germinal centre B cell-like (GC), activated B cell-like (ABC), and a "third" type. Expression of CD44 variant isoforms (CD44v) is associated with an unfavourable clinical outcome in DLBCL, but previous studies did not consider the clinicopathological heterogeneity of this disease.

Aims: To analyse the expression and prognostic significance of CD44 in DLBCL types.

Methods: A tissue microarray (TMA) comprising 90 DLBCLs was constructed. CD10, CD20, bcl-2, bcl-6, CD44 standard isoform (CD44s), and CD44v4, CD44v6, and CD44v9 were analysed immunohistochemically and correlated with clinical follow up.

Results: TMA expression of CD10, CD20, bcl-2, and bcl-6 showed 100% concordance with results from conventional sections in 60 cases. Samples were segregated into 22 GC (bcl-6+/CD10+/bcl-2-), 25 ABC (bcl-6-/CD10-/bcl-2+), and 35 unclassifiable DLBCLs. Overall survival (OS) at 30 months was 89%, 44%, and 58% in GC, ABC, and unclassified types, respectively. CD44v6 was coexpressed with bcl-2, appeared predominantly on bcl-6 negative cases, and correlated with disease stage. Cases negative for CD44s could be separated into CD44v6 negative (OS, 82% at 70 months) and CD44v6 positive (OS, 58%).

Conclusions: TMA technology is useful for immunophenotyping and clinicopathological analysis of large lymphoma populations. The GC phenotype of DLBCL is of independent prognostic significance for OS. Expression of CD44v6 correlates with disease stage, and might contribute to lymphoma dissemination. CD44v6 is expressed predominantly in ABC DLBCL, and in CD44 negative cases is associated with worse OS.

Keywords: diffuse large B cell lymphoma; CD44; prognosis; tissue microarray

Abbreviations: ABC, activated B cell-like; CD44s, CD44 standard isoform; CD44v, CD44 variant isoform; DLBCL, diffuse large B cell lymphoma; FFS, failure free survival; FL, follicular lymphoma; GC, germinal centre B cell-like; H&E, haematoxylin and eosin; IPI, international prognostic index; NHL, non-Hodgkin lymphoma; OS, overall cumulative survival; SLL, small lymphocytic lymphoma; TMA, tissue microarray

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Tzankov, A., Meier, C., Hirschmann, P., Went, P., Pileri, S. A., Dirnhofer, S. (2008). Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma. haematol 93: 193-200 [Abstract] [Full Text]  
• Obermann, E. C, Went, P., Tzankov, A., Pileri, S. A, Hofstaedter, F., Marienhagen, J., Stoehr, R., Dirnhofer, S. (2007). Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase. J. Clin. Pathol. 60: 794-797 [Abstract] [Full Text]  
• Zimpfer, A., Schonberg, S., Lugli, A., Agostinelli, C., Pileri, S. A, Went, P., Dirnhofer, S. (2007). Construction and validation of a bone marrow tissue microarray. J. Clin. Pathol. 60: 57-61 [Abstract] [Full Text]  
• Tzankov, A., Gschwendtner, A., Augustin, F., Fiegl, M., Obermann, E. C., Dirnhofer, S., Went, P. (2006). Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor standard treatment response and inferior outcome.. Clin. Cancer Res. 12: 2125-2132 [Abstract] [Full Text]