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Title: Activation and differentiation antigen expression by B-cell non-Hodgkin's lymphoma
Author: Salter, Donald McGovern
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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Over the last few years there has been an explosion of the knowledge of normal B cell physiology particularly in the area of control of B cell activation, proliferation and differentiation. This has been augmented by the availability of a large number of monoclonal antibodies (MCA) which recognise a wide range of molecules expressed at the cell surface by B cells at different stages of activation and differentiation. Non-Hodgkin's lymphomas are believed to result from the uncontrolled proliferation and accumulation of B cells arrested at different stages of differentiation. Currently used classifications of non-Hodgkin's lymphoma are based on this idea and morphologically equivalent normal and neoplastic cells may be identified. MCA which detect surface antigens on B cells may be used by immunohistological techniques to accurately phenotype both neoplastic and equivalent normal cells. Detailed phenotyping using a panel of antibodies may allow more accurate classification of non-Hodgkin's lymphoma and comparison with presumed normal equivalents. As many of the surface markers expressed by B cells have been shown to be involved with cell activation and proliferation it is possible that their expression may be important in uncontrolled growth and have prognostic significance. This investigation was undertaken in an attempt to evaluate the usefulness of detailed phenotyping in the pathological diagnosis and classification of non-Hodgkin's lymphoma and to evaluate the prognostic significance of antigens whose expression is associated with cell proliferation, activation and differentiation. The results show that there is extensive immunophenotypic heterogeneity in B cell lymphomas. Differences in antigen expression is present between cells of individual cases and between morphologically similar groups of tumours. Nevertheless certain patterns of antigen expression were identified. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas, CD5 expression being almost exclusive to lymphocytic and centrocytic groups. CD38, 4F2 antigen and CD71 were more often expressed by high grade lymphoma. There was a significant correlation with survival and expression of 4F2 antigen and CD71 (transferrin receptor). These may identify a poor prognostic group of cases in low grade lymphoma. The phenotypic heterogeneity exposed by detailed phenotyping creates difficulty for comparison with normal equivalents and mitigates against its use for diagnostic purposes. Phenotyping B cell non-Hodgkin's lymphoma for many of the antigens expressed at various stages of B cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications. A limited panel of antibodies against kappa, lambda, IgM, CD3, CD5, CD19, CD45 is sufficient for routine diagnostic purposes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available