MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study
Corresponding Author
Andrés J. M. Ferreri
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Correspondence: Andrés J. M. Ferreri, Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan 20132, Italy.
E-mail: [email protected]
Search for more papers by this authorTeresa Calimeri
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorPaolo Lopedote
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorIlaria Francaviglia
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorRita Daverio
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorChiara Iacona
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorCristina Belloni
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorSara Steffanoni
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAlessandro Gulino
Tumor Immunology Unit, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Search for more papers by this authorElena Anghileri
Molecular Neuro-Oncology Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Search for more papers by this authorAngelo Diffidenti
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAnnamaria Finardi
Clinical Neuroimmunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorFilippo Gagliardi
Neurosurgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorNicoletta Anzalone
Neuroradiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorAlessandro Nonis
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorRoberto Furlan
Clinical Neuroimmunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorDaniela De Lorenzo
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMaria R. Terreni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorVittorio Martinelli
Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarianna Sassone
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarco Foppoli
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorPiera Angelillo
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorElena Guggiari
Hematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAndrea Falini
Neuroradiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorPietro Mortini
Neurosurgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorMassimo Filippi
Vita-Salute San Raffaele University, Milan, Italy
Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorVittoria Tarantino
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarica Eoli
Molecular Neuro-Oncology Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Search for more papers by this authorFabio Ciceri
Vita-Salute San Raffaele University, Milan, Italy
Hematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorClaudio Doglioni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorClaudio Tripodo
Tumor Immunology Unit, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Search for more papers by this authorMassimo Locatelli
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMaria Giulia Cangi
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
These researchers shared the role of senior authors.
Search for more papers by this authorMaurilio Ponzoni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
These researchers shared the role of senior authors.
Search for more papers by this authorCorresponding Author
Andrés J. M. Ferreri
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Correspondence: Andrés J. M. Ferreri, Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan 20132, Italy.
E-mail: [email protected]
Search for more papers by this authorTeresa Calimeri
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorPaolo Lopedote
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorIlaria Francaviglia
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorRita Daverio
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorChiara Iacona
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorCristina Belloni
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorSara Steffanoni
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAlessandro Gulino
Tumor Immunology Unit, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Search for more papers by this authorElena Anghileri
Molecular Neuro-Oncology Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Search for more papers by this authorAngelo Diffidenti
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAnnamaria Finardi
Clinical Neuroimmunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorFilippo Gagliardi
Neurosurgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorNicoletta Anzalone
Neuroradiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorAlessandro Nonis
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorRoberto Furlan
Clinical Neuroimmunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorDaniela De Lorenzo
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMaria R. Terreni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorVittorio Martinelli
Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarianna Sassone
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarco Foppoli
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorPiera Angelillo
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorElena Guggiari
Hematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorAndrea Falini
Neuroradiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorPietro Mortini
Neurosurgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorMassimo Filippi
Vita-Salute San Raffaele University, Milan, Italy
Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorVittoria Tarantino
Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMarica Eoli
Molecular Neuro-Oncology Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Search for more papers by this authorFabio Ciceri
Vita-Salute San Raffaele University, Milan, Italy
Hematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorClaudio Doglioni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorClaudio Tripodo
Tumor Immunology Unit, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Search for more papers by this authorMassimo Locatelli
Division of Lab Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorMaria Giulia Cangi
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
These researchers shared the role of senior authors.
Search for more papers by this authorMaurilio Ponzoni
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
These researchers shared the role of senior authors.
Search for more papers by this authorSummary
Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
Conflict of interest
No conflicts of interest have been disclosed. Authors have not disclosed any financial relationships or other competing interests that could be perceived as biasing the study.
Supporting Information
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| bjh17357-sup-0001-Supinfo.docxWord document, 31.8 KB |
Table SI. Characteristics of controls. Table SII. Associations between molecular and clinical variables in patients with relapsed PCNSL. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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