Analysis of human equilibrative nucleoside transporter 1 (hENT1) protein in non-Hodgkin's lymphoma by immunohistochemistry

The human equilibrative nucleoside transporter 1 (hENT1) is a member of the equilibrative nucleoside transporter family that mediates cellular entry of gemcitabine, cytarabine, and fludarabine. Deficiency in hENT1 confers resistance to toxicity of these drugs in a variety of model systems. Since some nucleoside analogs have a role in treating patients with non-Hodgkin's lymphoma (NHL), this study was undertaken to assess hENT1 abundance in NHL. A total of 115 cases of NHL of various subtypes and 15 reactive lymph nodes were evaluated for the presence of hENT1 protein using immunohistochemistry applied to frozen tissues. Samples were considered positive when >= 50% of neoplastic cells showed immunostaining. In reactive lymph nodes, hENT1 was confined to the germinal centers, whereas mantle zone B-cells and interfollicular T-cells were negative. In NHL, a relatively high frequency of hENT1 positivity was found in Burkitt lymphoma/leukemia (63%), diffuse large B-cell lymphoma (DLCL; 45%), and follicular lymphoma (40%). In DLCL, 26% of cases were positive for CD10, and CD10-positive DLCL cases were more likely to be hENT1 positive than CD10-negative cases (P = 0.025). A lower frequency of hENT1 positivity was found in mantle cell lymphoma (13%) and peripheral T-cell lymphomas (37%). All marginal zone lymphomas (n = 5), chronic lymphocytic leukemia small lymphocytic lymphomas (n = 10), plasmacytoma (n = 3), acute lymphoblastic lymphoma/leukemia, and anaplastic large-cell lymphomas (n = 5) were negative. In conclusion, hENT1 was most frequently found in benign and malignant follicular center cells. Prospective studies to assess the value of hENT1 immunostaining in predicting resistance to nucleoside chemotherapy for NHL are warranted.