Bailey, Nigel Peter (1994) The biology of high and intermediate grade non-Hodgkin's lymphoma. University of Southampton, Doctoral Thesis.
Abstract
Intermediate and high grade non-Hodgkin's lymphomas (HIGNHL) are rare neoplasms of precursor T and B lymphocytes which are potentially curable with intensive chemotherapy. I have studied the clinical presentation of 265 such patients treated in uniform manner and examined the relationship between specific biological characteristics (vascularity, ploidy, proliferation (PCNA expression), macrophage, T cell and laminin infiltration) of the neoplasm with subsequent patient outcome. Widespread dissemination is one of the hallmarks of this disease which confers a poor prognosis. It has been suggested that the degree and site of spread may be determined by the cell surface characteristics of the primary tumour. Using immunohistochemistry (IHC), I have studied tumour cell antigen expression (LN-1 & 2, MB-2, MT-1, CD-3, UCHL1, L26) with respect to outcome in this group. The role of adhesion molecule expression (LFA-1 & 3, ICAM-1, VLA-4 & 6, CD44, Leu-8) was similarly explored in a subset of cases.
The following characteristics were significantly associated with a worse prognosis in univariate analysis:- age, stage, the presence of B symptoms, intra-abdominal, gut, lung, bone marrow or extra-lymphatic disease, liver and spleen involvement. When tumour characteristics were studied with respect to survival no significant correlation was demonstrated in relation to macrophage infiltration, tumour laminin content, vascularity, phenotype, ploidy nor antigen expression, other than PCNA expression which had a significantly negative association with survival. This large series extends our knowledge in demonstrating that PCNA staining has prognostic importance within HIGNHL. Positive associations were found between specific antigenic expression and certain involved disease sites providing a confirmatory suggestion of the role of adhesion molecules in the process of malignant lymphomatous dissemination e.g. lack of expression of LFA-1 is associated with liver disease and signifies a poor prognosis. Expression of CD44 was also correlated with greater disease dissemination and poor survival. A multivariate analysis demonstrated the following independent prognostic factors:- age, B symptoms, PCNA expression and the presence of extra-lymphatic and splenic disease. Based on this work, an alternative staging system focusing particularly on sites of disease involvement at presentation is suggested.
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