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Mol Cancer Res. 2017 May;15(5):541-552. doi: 10.1158/1541-7786.MCR-16-0301. Epub 2017 Jan 27.

Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas.

Author information

1
Haematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
2
Tumour Immunology Unit, Department of Health Science, Human Pathology Section University of Palermo School of Medicine, Palermo, Italy.
3
Unit of Diagnostic Haematopathology, European Institute of Oncology, Milan, Italy.
4
Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
5
Dermatology Unit, Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
6
Genetics and Genome Biology Paediatric Laboratory Medicine (PLM). The Hospital for Sick Children, Toronto, Ontario, Canada.
7
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
8
Histopathology, SRL Diagnostics, Mumbai, India.
9
Institute of Pathology, Medical University of Vienna, Vienna, Austria.
10
Department of Pathology, Portuguese Institute of Oncology, Lisbon, Portugal.
11
Hematopathology Section, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
12
Centro Diagnostico Italiano, Milano, Italy.
13
Unit of Diagnostic Haematopathology, European Institute of Oncology, Milan, Italy. stefano.pileri@ieo.it/stefano.pileri@unibo.it.
14
Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.

Abstract

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541-52. ©2017 AACR.

PMID:
28130401
DOI:
10.1158/1541-7786.MCR-16-0301
[Indexed for MEDLINE]
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