title: Expression of FoxO3a in clinical cases of malignant lymphoma.
abstract: Cancer-initiating cells (CICs) are a limited number of cells with tumorigenic activity. Few studies have been performed on CICs in malignant lymphoma. We recently demonstrated that a small number of FoxO3a-expressing cells possessed CIC-like potential in Hodgkin's lymphoma (HL) cell lines. In the present study, FoxO3a expression was examined immunohistochemically in 137 patients with malignant lymphoma. Among patients with HL, FoxO3a-positive tumor cells were detected in 11 of 11 with nodular sclerosis classical HL, 8 of 15 with mixed cellularity classical HL, 0 of 1 with lymphocyte-rich classical HL, and 2 of 3 with nodular lymphocyte-predominant HL. Only limited numbers of patients with non-HL expressed FoxO3a: 4 of 66 with diffuse large B-cell lymphoma, 1 of 20 with follicular lymphoma, and 1 of 5 with peripheral T-cell lymphoma, not otherwise specified. No FoxO3a expression was detected in patients with mantle cell lymphoma (n=3), extranodal marginal zone B-cell lymphoma (n=3), mediastinal large B-cell lymphoma (n=1), NK/T cell lymphoma (n=5), anaplastic large cell lymphoma (n=2), or T-lymphoblastic lymphoma/leukemia (n=2). These results suggest that FoxO3a is expressed mostly in patients with HL, but not in patients with non-HL. FoxO3a expression was limited to a small number of Hodgkin cells in a quiescent state. FoxO3a may be a CIC marker of HL, but not of non-HL.
authors.affiliation: Department of Pathology, Osaka University, Graduate School of Medicine, Yamada-oka 2-2, Suita 565-0871, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Ikeda
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hori
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Honma
authors.forename: Naoki
authors.initials: N
authors.lastname: Wada
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D016922:Cellular Senescence; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D051057:Proto-Oncogene Proteins c-akt
keywords: Cancer initiating cells; FoxO3a; Malignant lymphoma