Al-Alousi, Maha Noori Shakir; (1990) The lectins from European mistletoe (Viscum album): Isolation and detection of binding in primary breast cancer correlated with clinical behaviour. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis examines the place of Mistletoe plant extracts containing carbohydrate-binding proteins (lectins) in cancer treatment and their use as a tissue-based predictive test for biological behaviour of breast cancer. It begins with an account of the European Mistletoe (Viscum album), its mythology, history, use as an anti-cancer drug and the isolation and identification of 3 lectins. This is followed by an account of breast cancer, its problems of management and the value of prognostic factors. A review of lectin receptors in breast cancer is included. The practical work comprises: - Isolation and identification of 3 mistletoe lectins by gel, ion-exchange and affinity chromatography. Purity and molecular weight were determined by polyacrylamide gel electrophoresis while major carbohydrate specificity was determined by haemagglutination inhibition. Part of this work was carried out in East Berlin/GDR. - Raising rabbit polyclonal antibodies to the lectins. Determination of specificity by Ouchterlony gel diffusion, enzyme linked immunosorbent assay (ELISA), dot- and Western type immunoblotting. - Using the 3 isolated lectins to stain paraffin sections of 234 primary breast cancers, by a histochemical method. - Correlation of clinical behaviour with staining (lectin-binding) of sections, comparing histological type and size of primary, blood group, lymph node status, disease free interval (recurrence) and survival of 234 patients followed for up to 11 years. The lectins used showed major sugar specificities as follows: Mistletoe lectin I(MLI): Galactose Mistletoe lectin II(MLII): N-Acetyl-D-Galactosamine (Ga1NAc) Mistletoe lectin III(MLIII): Ga1NAc No significant correlation was seen between the binding of the 3 lectins to paraffin sections and histology type, grade, tumour size, blood group nor lymph node status. However, differences were seen between survival of stainers and non-stainers for each of the 3 lectins, especially MLIII, although this difference only just reached statistical significance (P less than 0.0441). A significant association between staining and recurrence was seen with all 3 lectins, in particular MLIII (P less than 0.0007), Having a major specificity for the sugar Ga1NAc. This result might suggest that primary breast cancers expressing this sugar are likely to metastasize sooner than cancers that do not. Detection of mistletoe lectins binding to receptors in primary breast cancer sections, and assessment of their role in behaviour of breast cancer does not appear to have been described before.

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