Immunohistochemistry for CCR4 C‐terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T‐cell leukemia/lymphoma
| Autor: | Atae Utsunomiya, Asahi Ito, Ayako Masaki, Keiichiro Fujii, Takashi Ishida, Takayuki Murase, Hiroshi Inagaki, Ryuzo Ueda, Shigeru Kusumoto, Yuma Sakamoto, Shinsuke Iida, Yukie Tashiro, Kentaro Yonekura |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Receptors CCR4 medicine.medical_treatment Clinical Decision-Making DNA Mutational Analysis Hematopoietic stem cell transplantation Antibodies Monoclonal Humanized medicine.disease_cause Adult T-cell leukemia/lymphoma Pathology and Forensic Medicine Antineoplastic Agents Immunological Protein Domains Predictive Value of Tests immune system diseases hemic and lymphatic diseases Biomarkers Tumor medicine Mogamulizumab Humans Leukemia-Lymphoma Adult T-Cell Survival rate Aged Mutation business.industry Patient Selection mogamulizumab Original Articles medicine.disease Immunohistochemistry Lymphoma Leukemia Treatment Outcome ATL Cancer research Biomarker (medicine) Original Article Female CCR4 prognosis business medicine.drug |
| Zdroj: | The Journal of Pathology: Clinical Research |
| ISSN: | 2056-4538 |
| DOI: | 10.1002/cjp2.180 |
| Popis: | Mogamulizumab targets extracellular N‐terminal domain of CCR4, which is expressed in most adult T‐cell leukemia/lymphoma (ATL) cases. Recently, we reported that CCR4 C‐terminal gain‐of‐function mutations were frequent in ATL cases, and a subgroup with these mutations who were treated without allogenic hematopoietic stem cell transplantation (HSCT) and with mogamulizumab‐containing [HSCT (−) and mogamulizumab (+)] regimens had a superior survival rate. Although these mutations are most likely a biomarker for predicting a strong response to mogamulizumab, their detection is time‐consuming and costly. A more convenient screening tool may be necessary in the clinical setting. In this study, the clinicopathological importance of immunohistochemistry for the CCR4 N‐terminus (CCR4‐N‐IHC) and C‐terminus (CCR4‐C‐IHC) was examined in a large ATL cohort (n = 92). We found that CCR4‐C‐IHC, but not CCR4‐N‐IHC, was inversely correlated with the CCR4 mutation status. In ATL patients negative for CCR4‐C‐IHC, a subgroup treated with HSCT (−) and mogamulizumab (+) regimens showed a significantly better prognosis. In addition, CCR4‐C‐IHC was found to be a useful marker for high‐sensitivity screening of the CCR4 mutational status (87%). The present study suggests that CCR4‐C‐IHC may be useful for identifying ATL patients harboring mutated CCR4 who may benefit from the superior efficacy of mogamulizumab‐containing regimens and that CCR4‐C‐IHC may be a rapid and cost‐efficient tool for screening for CCR4 mutation status. |
| Databáze: | OpenAIRE |
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