TY - JOUR
T1 - MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma
T2 - results from a prospective study
AU - Ferreri, Andrés J.M.
AU - Calimeri, Teresa
AU - Lopedote, Paolo
AU - Francaviglia, Ilaria
AU - Daverio, Rita
AU - Iacona, Chiara
AU - Belloni, Cristina
AU - Steffanoni, Sara
AU - Gulino, Alessandro
AU - Anghileri, Elena
AU - Diffidenti, Angelo
AU - Finardi, Annamaria
AU - Gagliardi, Filippo
AU - Anzalone, Nicoletta
AU - Nonis, Alessandro
AU - Furlan, Roberto
AU - De Lorenzo, Daniela
AU - Terreni, Maria R.
AU - Martinelli, Vittorio
AU - Sassone, Marianna
AU - Foppoli, Marco
AU - Angelillo, Piera
AU - Guggiari, Elena
AU - Falini, Andrea
AU - Mortini, Pietro
AU - Filippi, Massimo
AU - Tarantino, Vittoria
AU - Eoli, Marica
AU - Ciceri, Fabio
AU - Doglioni, Claudio
AU - Tripodo, Claudio
AU - Locatelli, Massimo
AU - Cangi, Maria Giulia
AU - Ponzoni, Maurilio
N1 - Funding Information:
This was an academic study supported in part by an independent grant from ?Roche Award for Younger Researchers 2018? (assigned to Teresa Calimeri; there is no award number). Neither the sponsor (IRCCS San Raffaele Scientific Institute, Milano, Italy) nor the grant provider had any role in the design, data collection, analysis, results interpretation and writing of the report. Article was written by the first and senior authors. Ferreri AJM, as corresponding author, had full access to all the data in the study and had final responsibility for the decision to submit for publication. The authors are indebted to our patients and their families for their generous commitment. We also acknowledge haematologists, oncologists, pathologists, neurologists, neuroradiologists, neurosurgeons, research nurses, and data managers from the IRCCS San Raffaele Scientific Institute, Milan, Italy.
Publisher Copyright:
© 2021 British Society for Haematology and John Wiley & Sons Ltd
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - diffuse large B-cell lymphoma
KW - interleukin-10
KW - interleukin-6
KW - MYD88 L265P mutation
KW - primary CNS lymphoma
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U2 - 10.1111/bjh.17357
DO - 10.1111/bjh.17357
M3 - Article
C2 - 33620087
AN - SCOPUS:85101240933
SN - 0007-1048
VL - 193
SP - 497
EP - 505
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -