Open AccessDe novo diffuse large B ‐cell lymphoma with a CD 20 immunohistochemistry‐positive and flow cytometry‐negative phenotype: Molecular mechanisms and correlation with rituximab sensitivity
Author(s) -
Tokunaga Takashi,
Tomita Akihiro,
Sugimoto Keiki,
Shimada Kazuyuki,
Iriyama Chisako,
Hirose Tatsuya,
ShirahataAdachi Mizuho,
Suzuki Yasuhiro,
Mizuno Hiroki,
Kiyoi Hitoshi,
Asano Naoko,
Nakamura Shigeo,
Kinoshita Tomohiro,
Naoe Tomoki
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12307
Subject(s) - cd20 , immunohistochemistry , rituximab , flow cytometry , lymphoma , immunophenotyping , b cell , cd19 , antibody , pathology , cancer research , phenotype , microbiology and biotechnology , biology , medicine , immunology , gene , biochemistry
CD20 is expressed in most B‐cell lymphomas and is a critical molecular target of rituximab. Some B ‐cell lymphomas show aberrant CD 20 expression, and rituximab use in these patients is controversial. Here we show both the molecular mechanisms and the clinical significance of de novo diffuse large B ‐cell lymphomas (DLBCL) that show a CD 20 immunohistochemistry ( IHC )‐positive and flow cytometry ( FCM )‐ negative (IHC[+]/FCM[−]) phenotype. Both IHC and FCM using anti‐ CD 20 antibodies L 26 and B 1, respectively, were analyzed in 37 of the 106 cases of de novo DLBCL ; 8 (22%) of these cases were CD 79a(+)/ CD 20(+) with IHC and CD 19(+)/ CD 20(−) with FCM . CD20 ( MS4A1 ) mRNA expression was significantly lower in IHC (+)/ FCM (−) cells than in IHC (+)/ FCM (+) cells ( P = 0.0005). No genetic mutations were detected in MS4A1 promoter and coding regions. Rituximab‐mediated cytotoxicity in the CDC assay using IHC (+)/ FCM (−) primary cells was significantly lower than in IHC (+)/ FCM (+) cells ( P < 0.05); however, partial effectiveness was confirmed. FCM using rituximab detected CD 20 more efficiently than B 1. No significant difference was observed between IHC (+)/ FCM (−) and IHC (+)/ FCM (+) patients in overall survival ( P = 0.664). Thus, lower expression of CD20 mRNA is critical for the CD 20 IHC (+)/ FCM (−) phenotype. Lower CD 20 expression with FCM does not rule out rituximab use in these patients if expression is confirmed with IHC . FCM using rituximab may be more informative than B 1 for predicting rituximab effectiveness in IHC (+)/ FCM (−) cases.