Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing.
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.
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Luisa
L
Lorenzi
Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
Claudia
C
Döring
Genecore, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Tobias
T
Rausch
Genecore, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Vladimir
V
Benes
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Silvia
S
Lonardi
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Mattia
M
Bugatti
Haematopathology Section, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Elias
E
Campo
Department of Pathology, Portuguese Institute of Oncology, Lisbon, Portugal.
José
J
Cabeçadas
Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Ingrid
I
Simonitsch-Klupp
Histopathology, SRL Diagnostics, Mumbai, India.
Anita
A
Borges
Histopathology, SRL Diagnostics, Mumbai, India.
Jay
J
Mehta
Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Claudio
C
Agostinelli
Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.|Unit of Diagnostic Haematopathology, European Institute of Oncology, Milan, Italy.
Stefano Aldo
SA
Pileri
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Fabio
F
Facchetti
Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
Martin-Leo
ML
Hansmann
Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
Sylvia
S
Hartmann
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D054740:Dendritic Cell Sarcoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D059467:Transcriptome; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; C465580:FDCSP protein, human; D011506:Proteins; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin
follicular dendritic cell sarcoma; follicular dendritic cell-secreted protein; immunohistochemistry; serglycin; whole transcriptome sequencing