Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P-STAT3 in primary central nervous sys
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ORIGINAL ARTICLE
Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P‑STAT3 in primary central nervous system diffuse large B‑cell lymphomas Dabei Tang1 · Wenjia Su2 · Xiaowei Wang1 · Zhong Chu1 · Lei Zhang1 · Jin Zhou2 · Qingyuan Zhang1 Received: 13 August 2020 / Accepted: 6 October 2020 © The Japan Society of Brain Tumor Pathology 2020
Abstract Patients with primary central nervous system lymphoma (PCNSL) have a prognosis poorer than that of systemic lymphoma patients. In patients with this condition, TLR4/STAT3 pathway alterations and the MYD88 L265P mutation may be viable targets for therapeutic intervention. The present study was, therefore, designed to identify clinicopathologic correlates of MYD88 mutations and TLR4/STAT3 pathway alterations in PCNSL. We detected TLR4 and p-STAT3 in 41.5% (22/53) and 43.4% (23/53) of PCNSL patients, respectively, while 60.4% of these patients (32/53) were found to harbor the MYD88 L265P mutation. TLR4 expression was found to be significantly associated with the presence of multiple brain lesions, while p-STAT3 expression was significantly linked to advanced age, the presence of multiple brain lesions, non-GCB histological findings, and non-CR status. The presence of the MYD88 L265P mutation was significantly linked to advanced age, the presence of multiple brain lesions, and DLBCL molecular subtype. Multivariate analyses additionally confirmed that elevated TLR4 and p-STAT3 expression levels are associated with a poorer PCNSL patient prognosis. Based on these findings, we hypothesize that signaling through the TLR4/MYD88/STAT3 pathway plays a key role in the pathogenesis of PCNSL. Keywords TLR4 · MYD88 L265P mutation · P-STAT3 · PCNSL
Instruction Primary central nervous system lymphoma (PCNSL) is a rare form of invasive extranodal non-Hodgkin lymphoma that is not systemic and is instead restricted to the brain, spinal cord, eyes, and/or leptomeningeal compartments. Over 95% of PCNSL cases are of the diffuse large B-cell lymphoma (DLBCL) subtype. Relative to patients suffering Dabei Tang and Wenjia Su made the same contribution to the paper, and should be recognized as co-first authors. * Jin Zhou [email protected] * Qingyuan Zhang [email protected] 1
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road No. 150, Harbin, Heilongjiang 150081, People’s Republic of China
Department of Medical Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China
2
from peripheral DLBCL, however, these PCNSL patients exhibit disease that is generally more aggressive, refractory to chemotherapy, and associated with poorer clinical outcomes [1]. The identification of novel therapeutic targets is, therefore, essential to improve PCNSL patient prognosis. Toll-like receptors (TLRs) are essential innate immune pattern recognition receptors that facilitate the rapid detection of pathogens. TLR4, which was the first human TLR to be identified, can en
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