title: FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma.
abstract: FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL.
authors: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Tatsuya
authors: T
authors: Nishi
authors: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Hiroyuki
authors: H
authors: Takahashi
authors: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Miki
authors: M
authors: Hashimura
authors: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Tsutomu
authors: T
authors: Yoshida
authors: Division of Cell Biology, Department of Biosciences, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Yasutaka
authors: Y
authors: Ohta
authors: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Makoto
authors: M
authors: Saegusa
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism; D005260:Female; D064448:Filamins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000401:mortality*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality*; D016411:Lymphoma, T-Cell, Peripheral / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: C497033:ARHGAP24 protein, human; D014408:Biomarkers, Tumor; D018821:CD18 Antigens; C489850:ECT2 protein, human; C578663:FLNA protein, human; D064448:Filamins; D020690:GTPase-Activating Proteins; D011518:Proto-Oncogene Proteins
keywords: B-lymphocyte; FilGAP; Rac; follicular lymphoma; prognosis
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