Open AccessImmunohistochemistry for CCR4 C‐terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T‐cell leukemia/lymphoma
Author(s) -
Fujii Keiichiro,
Sakamoto Yuma,
Masaki Ayako,
Murase Takayuki,
Tashiro Yukie,
Yonekura Kentaro,
Utsunomiya Atae,
Ito Asahi,
Kusumoto Shigeru,
Iida Shinsuke,
Ueda Ryuzo,
Ishida Takashi,
Inagaki Hiroshi
Publication year - 2021
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.180
Subject(s) - ccr4 , immunohistochemistry , medicine , lymphoma , leukemia , oncology , cancer research , immunology , receptor , chemokine receptor , chemokine
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.