Diss, Timothy Charles; (1996) The polymerase chain reaction in the charaterisation and diagnosis of lymphomas. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The polymerase chain reaction (PCR) offers a practical means of studying the clonality and molecular genetic abnormalities of lymphocyte populations in histological tissue samples. This may provide an important tool in the diagnosis and characterisation of lymphoproliferative disorders, which are often difficult to assess using morphological and immunophenotypic techniques. In this thesis, clonality analyses of lymphoid infiltrates, by PCR amplification of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) β and γ chain genes, were evaluated in terms of their specificity, sensitivity and applicability to routinely processed histological samples. Lymphomas, benign lymphoid infiltrates and equivocal lesions, particularly from extra-nodal sites, were examined. Optimised PCR procedures were used to study tumour progression and clonality of low grade extra-nodal B-cell lymphomas and nodular lymphocyte predominance Hodgkin's disease (NLPHD). The role of PCR detection of the lymphoma type specific chromosomal translocations t(14;18) and t(11;14), in the diagnosis and classification of low grade lymphomas was assessed. PCR analysis of clonality, t(14;18), Helicobacter pylori and Epstein Barr virus was carried out in a comprehensive study of myoepithelial sialadenitis (MESA) and low grade B-cell mucosa associated lymphoid tissue (MALT) lymphoma of the parotid. PCR demonstration of monoclonality was shown to be useful in discriminating benign from malignant B- and T-lineage lymphoproliferations in morphologically equivocal cases, and to be applicable to routine tissue samples. PCR analysis showed that a single clone was involved at multiple sites during progression of a low grade B-cell MALT lymphoma. PCR results suggested that NLPHD is a polyclonal B-cell disorder, but no clonal relationship between this disease and subsequent high grade lymphoma was demonstrated. T(14;18) and t(11;14) chromosome translocations were shown to be detectable by PCR in routine specimens and were largely restricted to follicular and mantle cell lymphomas respectively, but the usefulness of the technique in classification may be limited by the absence of characterised translocations in a high proportion of cases. PCR analysis of clonality in lymphoid infiltrates of the parotid supported previous histological descriptions of the development of low grade B-cell lymphoma at this site. No strong links between MALT lymphoma of the parotid and t(14;18), Helicobacter pylori and Epstein Barr virus were found.

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