Abstract 2997: Peripheral T-cell lymphomas not otherwise specified correspond to distinct mature T-cell populations basing on the global gene expression profile
Authors: Piccaluga Pier-Paolo , Agostinelli Claudio , Rossi Maura , Tripodo Claudio , Gibellini Davide , Sapienza Maria Rosaria , Laginestra Maria-Antonella , Gazzola Anna , Pileri Stefano Aldo 
Published: August 2012

Abstract
Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are the commonest T-cell neoplasms. Recent studies suggested that different PTCL/NOS subgroups might be identified according to a diverse cellular derivation or correspondence to various cellular counterparts. However, so far, it was possible only to discriminate T-helper (TH) vs. T-cytotoxic (TC) tumors. Noteworthy, due to their typical aberrant phenotype, such distinction could be effectively performed only by gene expression profiling (GEP). In addition, further distinctions (i.e. TH subtypes) were only occasionally described in scattered cases. In this study, we aimed to define the counterparts of PTCLs/NOS based on their global GEP. We generated and analyzed GEP from 108 PTCLs/NOS by using either Affymetrix HG-U133 2.0 plus microarray (N=28 cases) or Illumina whole genome DASL assay (N=80). The two groups corresponded to fresh/frozen samples and formalin fixed paraffin embedded (FFPE) ones, respectively. Tissue microarrays (TMAs) were built including the same cases, and immunohistochemistry (IHC) was used for candidate markers validation. The molecular signatures of T-cell subsets (Th1, Th2, Th17, T-follicular helper/Tfh, Treg, T-central memory/Tcm, T-effector memory/Tem, and T-cytotoxic/TC) were studied in the tumor samples using previously validated cell classifiers as well as gene set enrichment analysis (GSEA). First, we studied the 28 samples for which fresh/frozen biopsies were available. We found that 23/28 corresponded to TH and 5/28 to TC cells. Moreover, the TH were more related to Th1 (18/23) rather then to Th2 (1/23) cells, in 4 instances not being a significant enrichment in neither one signature. When further signatures were tested, we found that PTCLs/NOS were more frequently related to Tcm cells (12/23), than to Tem (5/23), Tfh (2/23), Treg (0/23), or Th17 (0/23). Four again presented no significant similarity with the studied populations. We then tested whether reliable profiles could be obtained from FFPE samples. Notably, we could assign 66/80 (83%) cases to a specific counterpart. In particular, 42/80 were TH, while 24/80 were TC. At further analysis, the TH cases were first classified as Th1 (N=21) or Th2 (N=13) and then as Tcm (N=20), Tem (N=7), Tfh (N=4) or Treg (N=2), 1 not being further classified. IHC confirmed the genomic data as far as Tfh and Treg markers were concerned, not being available, at present, consistent IHC markers for Th1, Th2, Tcm and Tem. Conversely, it was inadequate to distinguish TH and TC, due to the frequent lack of CD4, CD8 and other cytotoxic molecules. In conclusion, we showed that PTCL/NOS heterogeneity is largely due to the correspondence to different counterparts and confirmed our previous observation that GEP is probably more effective than IHC for the sub classification of this tumor type.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2997. doi:1538-7445.AM2012-2997