Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing
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Luisa Lorenzi1, Claudia Döring2, Tobias Rausch3, Vladimir Benes3, Silvia Lonardi1, Mattia Bugatti1, Elias Campo4, José Cabeçadas5, Ingrid Simonitsch-Klupp6, Anita Borges7, Jay Mehta7, Claudio Agostinelli8, Stefano Aldo Pileri8,9, Fabio Facchetti1, Martin-Leo Hansmann2, Sylvia Hartmann2
1Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
2Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany
3Genecore, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
4Haematopathology Section, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
5Department of Pathology, Portuguese Institute of Oncology, Lisbon, Portugal
6Institute of Pathology, Medical University of Vienna, Vienna, Austria
7Histopathology, SRL Diagnostics, Mumbai, India
8Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
9Unit of Diagnostic Haematopathology, European Institute of Oncology, Milan, Italy
Luisa Lorenzi, email: firstname.lastname@example.org
Keywords: follicular dendritic cell sarcoma, whole transcriptome sequencing, immunohistochemistry, follicular dendritic cell-secreted protein, serglycin
Received: September 16, 2016 Accepted: January 17, 2017 Published: January 27, 2017
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.
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