Shingo Takano1, Keiichiro Hattori2, Eiichi Ishikawa3, Yoshitaka Narita4, Yasuo Iwadate5, Fumio Yamaguchi6, Motoo Nagane7, Jiro Akimoto8, Hidehiro Oka9, Satoshi Tanaka10, Mamiko Sakata2, Masahide Matsuda3, Tetsuya Yamamoto3, Shigeru Chiba2, Akira Matsumura3. 1. Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: shingo4@md.tsukuba.ac.jp. 2. Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. 3. Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. 4. Department of Neurosurgery and Neuro-Oncology, National Cancer Center, Tokyo, Japan. 5. Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. 6. Department of Neurological Surgery, Nippon Medical School, Tokyo, Japan. 7. Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan. 8. Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan. 9. Department of Neurosurgery, Kitasato University School of Medicine, Kanagawa, Japan. 10. Department of Neuro-Oncology and Neurosurgery, Tokyo Nishi Tokushukai Hospital, Tokyo, Japan.
Abstract
BACKGROUND: Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. METHODS: Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing. RESULTS: The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). CONCLUSION: The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients.
BACKGROUND: Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. METHODS: Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88L265P mutation was evaluated by polymerase chain reaction and direct sequencing. RESULTS: The MyD88L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). CONCLUSION: The MyD88L265P mutation predicted a poor prognosis in elderly PCNSLpatients. A new tailor-made treatment strategy might be needed for these patients.
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