Journal
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
Volume 7, Issue 1, Pages 52-60Publisher
WILEY
DOI: 10.1002/cjp2.180
Keywords
ATL; CCR4; immunohistochemistry; mogamulizumab; prognosis
Categories
Funding
- Japan Agency for Medical Research and Development [17K08746, 16H04713, 17ck0106287h0001, 16cm0106301h0001, 15ck0106132h0002]
- Aichi Cancer Research Foundation
- Nitto Foundation
- [20K16177]
- Grants-in-Aid for Scientific Research [17K08746] Funding Source: KAKEN
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CCR4-C-IHC may be a useful tool for predicting response to mogamulizumab in ATL patients and screening for CCR4 mutation status.
Mogamulizumab targets extracellular N-terminal domain of CCR4, which is expressed in most adult T-cell leukemia/lymphoma (ATL) cases. Recently, we reported thatCCR4C-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 theCCR4mutation 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 theCCR4mutational status (87%). The present study suggests that CCR4-C-IHC may be useful for identifying ATL patients harboring mutatedCCR4who 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 forCCR4mutation status.
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