Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.
In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL 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 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-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 PCFCCLs and PCLBCLs-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 PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.
Department of Dermatology, B1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Juliette J
JJ
Hoefnagel
Remco
R
Dijkman
Katia
K
Basso
Patty M
PM
Jansen
Christian
C
Hallermann
Rein
R
Willemze
Cornelis P
CP
Tensen
Maarten H
MH
Vermeer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007866:Leg / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology