CD44 VARIANT ISOFORMS IN NON-HODGKINS-LYMPHOMA - A NEW INDEPENDENT PROGNOSTIC FACTOR

Isoforms of the transmembrane glycoprotein CD44, generated by alternat ive RNA splicing, have been correlated to tumor dissemination, For eva luation of the potential role of CD44 variant isoforms in non-Hodgkin' s lymphoma (NHL), the presence of CD44 isoforms was analyzed in a larg e panel of reactive and neoplastic lymphoid tissues by immunohistochem ical staining, as well as detection of CD44 variant RNAs by the revers e transcriptase-polymerase chain reaction. Whereas the CD44 standard o r hematopoietic isoform (CD44s), devoid of the variant regions, was ex pressed in all leukocyte subpopulations, the variant isoforms (CD44v) showed a highly restricted pattern of expression, mainly observed in e pithelial layers of lymphoid tissues and subpopulations of leukocytes after stimulation. In addition to a strong expression of CD44s, varian t 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). More over, multivariate analysis indicated CD44-6v as a new independent pro gnostic 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). (C) 1995 by The American Society of Hema tology.