Haematologica, Vol 94, Issue 11, 1555-1562 doi:10.3324/haematol.2009.010264
Copyright © 2009 by Ferrata Storti Foundation
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Malignant Lymphomas

SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype

Ana Mozos1, Cristina Royo1, Elena Hartmann2, Daphne De Jong3, Cristina Baró4, Alexandra Valera1, Kai Fu5, Dennis D. Weisenburger5, Jan Delabie6, Shih-Sung Chuang7, Elaine S. Jaffe8, Carmen Ruiz-Marcellan9, Sandeep Dave10, Lisa Rimsza11, Rita Braziel12, Randy D. Gascoyne13, Francisco Solé4, Armando López-Guillermo1, Dolors Colomer1, Louis M. Staudt8, Andreas Rosenwald14, German Ott14, Pedro Jares1, Elias Campo1

1 Hematopathology Section, Department of Pathology and Hematology, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain
2 Institute of Pathology, University of Würzburg, Würzburg, Germany
3 Department of Pathology, The Netherlands Cancer Institute/Antoni von Leevenhoek Hospital, Amsterdam, The Netherlands
4 Laboratory of Molecular Cytogenetics, Department of Pathology, Hospital del Mar, Barcelona, Spain
5 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha
6 Department of Pathology, Norwegian Radium Hospital, Olso, Norway
7 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
8 Section of Hematopathology and Lymphoma Clinical Research, Center for Cancer Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, USA
9 Department of Pathology, Vall d’Hebron University Hospital, Autonomous University of Barcelona, Spain
10 Duke Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA
11 Department of Pathology, The University of Arizona College of Medicine, Tucson, Arizona, USA
12 Department of Pathology, Oregon Health and Science University, USA
13 Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada
14 Institut für Klinische Pathologie, Robert-Bosch-Krankenhaus, Stuttgart, Germany

Correspondence: Elias Campo, MD, PhD. Department of Pathology, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain. E-mail:ecampo{at}clinic.ub.es

Background: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

Design and Methods: The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin D1-negative mantle cell lymphoma, 54 cases of conventional mantle cell lymphoma, and 209 additional lymphoid neoplasms.

Results: SOX11 mRNA was highly expressed in conventional and cyclin D1-negative mantle cell lymphoma and in 33% of the cases of Burkitt’s lymphoma but not in any other mature lymphoid neoplasm. SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt’s lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms. Cyclin D2 and D3 mRNA levels were significantly higher in cyclin D1-negative mantle cell lymphoma than in conventional mantle cell lymphoma but the protein expression was not discriminative. The clinico-pathological features and outcomes of the patients with cyclin D1-negative mantle cell lymphoma identified by SOX11 expression were similar to those of patients with conventional mantle cell lymphoma.

Conclusions: SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma.

Key words: mantle cell lymphoma, cyclin D1, SOX11.


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S. A. Pileri and B. Falini
Mantle cell lymphoma
Haematologica, November 1, 2009; 94(11): 1488 - 1492.
[Full Text] [PDF]