Stauder R, Eisterer W, Thaler J, Günthert U
Basel Institute for Immunology, Switzerland.
Blood. 1995 May 15;85(10):2885-99.
Isoforms of the transmembrane glycoprotein CD44, generated by alternative RNA splicing, have been correlated to tumor dissemination. For evaluation of the potential role of CD44 variant isoforms in non-Hodgkin's lymphoma (NHL), the presence of CD44 isoforms was analyzed in a large panel of reactive and neoplastic lymphoid tissues by immunohistochemical staining, as well as detection of CD44 variant RNAs by the reverse transcriptase-polymerase chain reaction. Whereas the CD44 standard or hematopoietic isoform (CD44s), devoid of the variant regions, was expressed in all leukocyte subpopulations, the variant isoforms (CD44v) showed a highly restricted pattern of expression, mainly observed in epithelial layers of lymphoid tissues and subpopulations of leukocytes after stimulation. In addition to a strong expression of CD44s, variant isoforms containing CD44-6v in combination with other variant exons were observed predominantly in aggressive lymphoma and were associated with a shorter overall survival of patients (n = 138; P < .0001). Moreover, multivariate analysis indicated CD44-6v as a new independent prognostic parameter in high grade NHL in comparison with the risk groups defined by the International NHL Lymphoma Prognostic Factors Project (N Engl J Med 329:987, 1993).
由可变RNA剪接产生的跨膜糖蛋白CD44的异构体与肿瘤扩散相关。为了评估CD44变异异构体在非霍奇金淋巴瘤（NHL）中的潜在作用，通过免疫组织化学染色在大量反应性和肿瘤性淋巴组织中分析了CD44异构体的存在情况，并通过逆转录聚合酶链反应检测了CD44变异RNA。缺乏变异区域的CD44标准型或造血异构体（CD44s）在所有白细胞亚群中均有表达，而变异异构体（CD44v）表现出高度受限的表达模式，主要见于淋巴组织的上皮层以及刺激后的白细胞亚群。除了CD44s的强表达外，包含CD44-6v并与其他变异外显子结合的变异异构体主要在侵袭性淋巴瘤中观察到，并且与患者较短的总生存期相关（n = 138；P <.0001）。此外，多变量分析表明，与国际NHL淋巴瘤预后因素项目定义的风险组相比（《新英格兰医学杂志》329:987, 1993），CD44-6v是高级别NHL的一个新的独立预后参数。
