CCR4 is rarely expressed in CCR4-mutated T/NK-cell lymphomas other than adult T-cell leukemia/lymphoma

CCR4 is expressed on tumor cells of most patients with adult T-cell leukemia/lymphoma (ATL). Gain-of-function mutations of the CCR4 gene in ATL patients may be associated with alterations at the carboxyl terminus, a finding which led to a high efficacy anti-CCR4 antibody, mogamulizumab. Only a few studies have reported CCR4 protein expression and genomic CCR4 mutations in non-ATL T/NK-cell lymphomas. Furthermore, an association between CCR4 protein expression, genomic CCR4 mutations, and transcript CCR4 mutations has not been well analyzed. The T/NK-cell lymphomas (n = 226) enrolled in this study were examined for CCR4 expression by immunohistochemistry. CCR4 mutations in the codons 322-348 were detected by direct sequencing and a SNaPshot Multiplex assay. CCR4 protein expression was positive in 48/52 (92%) and 58/174 (33%) of ATL and non-ATL cases, respectively, and genomic CCR4 mutations were detected in 17/52 (33%) and 6/174 (3.4%), respectively. While all 17 ATL cases with genomic CCR4 mutations were positive for CCR4 protein expression, five of six mutated non-ATL cases were negative for CCR4 protein expression and transcript CCR4 mutations. This study suggests that frequencies of CCR4 expression and genomic CCR4 mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas.