Rawal Yeshwant B, Nuovo Gerard J, Frambach Gwyn E, Porcu Pierluigi, Baiocchi Robert A, Magro Cynthia M
Department of Oral and Maxillofacial Pathology, The Ohio State University, Athens, 43210, USA.
J Cutan Pathol. 2005 Oct;32(9):616-21. doi: 10.1111/j.0303-6987.2005.00305.x.
Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported.
Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available.
Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology.
Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.
自1997年以来,利妥昔单抗一直用于治疗复发的低度或晚期非霍奇金淋巴瘤,其作用靶点为B细胞表达的CD20抗原。单药利妥昔单抗治疗安全且耐受性良好。有报道称,利妥昔单抗治疗后出现CD20表达缺失的复发情况。
4例CD20阳性皮肤B细胞淋巴瘤患者接受利妥昔单抗治疗后复发。对活检组织进行细胞质CD20表达评估;若有可用组织,也对CD20信使核糖核酸进行评估。
在最后一剂利妥昔单抗后1.5至3个月内发生的皮肤复发为CD20阴性。在3例病例中,随后的复发显示CD20重新表达。那些通过免疫组织化学显示表面和细胞质CD20缺失的活检组织,使用基于原位聚合酶链反应的方法也未显示CD20信使核糖核酸的证据。
利妥昔单抗可能与CD20阴性B细胞克隆的出现有关,这可能使肿瘤对该药物不敏感。相反,在停药后,肿瘤细胞内可能会出现CD20的重新表达,从而允许使用这种单克隆抗体进行治疗干预。CD20表达的缺失似乎是该药物对CD20信使核糖核酸合成的直接作用。