Blood, 1 May 2005, Vol. 105, No. 9, pp. 3671-3678.
Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-04-1594.
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Submitted April 28, 2004
Accepted August 1, 2004
Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling
Juliette J Hoefnagel, Remco Dijkman, Katia Basso, Patty M Jansen, Christian Hallermann, Rein Willemze*, Cornelis P Tensen, and Maarten H Vermeer
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
Institute for Cancer Genetics, Columbia University, New York, New York, USA
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Department of Dermatology, University Hospital Goettingen, Goettingen, Germany
* Corresponding author; email: willemze.dermatology{at}lumc.nl.
In the EORTC classification two types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and primary cutaneous large B-cell lymphomas of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival >95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted.
To establish a molecular basis for this subdivision in the EORTC classification we investigated the gene expression profiles of 21 PCLBCL by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into two distinct subgroups consisting of respectively 8 PCFCCL and 13 PCLBCL-leg. PCLBCL-leg showed increased expression of genes associated with cell proliferation, the proto-oncogenes Pim-1, Pim-2 and c-Myc, and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCL and PCLBCL-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCL and PCLBCL-leg and provide molecular support for the subdivision used in the EORTC classification.
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