Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing.

Luisa Lorenzi,Jay Mehta,Ingrid Simonitsch-Klupp,Stefano Aldo Pileri,Claudio Agostinelli,Elias Campo,Tobias Rausch,Fabio Facchetti,Mattia Bugatti,Claudia Döring,Silvia Lonardi,José Cabeçadas,Martin-Leo Hansmann,Sylvia Hartmann,Anita Borges,Vladimir Benes

doi:10.18632/oncotarget.14864

Abstract

Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas. FDC secreted protein (FDCSP) and Serglycin (SRGN) proved to be specific markers of FDC and related tumor. They showed better specificity and sensitivity values than some well known markers used in FDC sarcoma diagnosis (specificity: 98.6%, and 100%, respectively; sensitivity: 72.73% and 68.18%, respectively). In our cohorts CXCL13, CD21, CD35, FDCSP and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis. In summary, by WTS we identified two novel FDC markers and by the analysis of a wide cohort of cases and controls we propose an efficient marker panel for the diagnosis of this rare and enigmatic tumor.

Highlights

Follicular dendritic cell sarcoma (FDC-S) is the neoplastic proliferation of follicular dendritic cells (FDC) [1,2]
In our cohorts CXCL13, CD21, CD35, FDC secreted protein (FDCSP) and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis
FDC belong to the stromal compartment of secondary lymphoid organs [3] and share crucial interaction capacities with the haematopoietic counterpart; both quality and effectiveness of immune responses depend from their integrity [4,5,6]

Summary

Introduction

Follicular dendritic cell sarcoma (FDC-S) is the neoplastic proliferation of follicular dendritic cells (FDC) [1,2]. FDC belong to the stromal compartment of secondary lymphoid organs [3] and share crucial interaction capacities with the haematopoietic counterpart; both quality and effectiveness of immune responses depend from their integrity [4,5,6]. FDC-S is included in the WHO classification of Haematopoietic tumors [1] and not in the WHO classification of Tumors of Soft Tissue and Bone [7] despite of its mesenchymal www.impactjournals.com/oncotarget origin. The complex mechanisms mediating these functions are still largely unknown but new insights have been recently achieved in experimental models [4, 8,9,10]. Its behavior is unpredictable; in a recent large review study, local recurrence and distant metastasis were reported to be equal to 28.1% and 27.2%, respectively [12]

Methods

Results

Conclusion