Variations of binding of labelled tumor necrosis factor alpha, epidermal growth factor, ganglioside GM-1 and N-cetylglucosamine,galactoside-specific mistletoe lectin and lectinspecific antibodies in mesothelioma and metastatic adenocarcinoma of the pleura

Journal/Book: Lung-Cancer 8 (3-4), 185-192. 1992;

Abstract: Cytokines, growth factors, biologically active carbohydrate ligands andgrowth-related lectins like calcyclin or the heparin-binding lectin aremonitored for their potential in differential diagnosis. Since thegalactoside-specific mistletoe lectin enhances cytokine secretion invitro and in vivo, presence of its ligands on tumor and inflammatorycells is monitored. Tumor necrosis factor alpha (TNF-alpha), epidermalgrowth factor (EGF), and mistletoe lectin (ML-1) as well ascarrier-immobilized ganglioside GM1 (GM-1), and N-acetyl-D-glucosamine(GlcNAc) were biotinylated, and applied to formalin-fixed,paraffin-embedded surgical specimens of 30 cases with epithelialmesothelioma of the pleura, 20 cases with nonspecific acute pleuritis,and 22 cases with metastatic adenocarcinoma into the pleura. Inaddition, polyclonal antibodies that are specific for calcyclin and theheparin-binding lectin, respectively, were applied to the same cohorts.Statistically significant differences (p < 0.05) were obtained in thepercentage of positive cases for the probes GM-1 and GlcNAc betweenmesothelioma and metastatic adenocarcinoma: 67% of mesothelioma casesstained positively to GM-1, but only 32% of the adenocarcinoma cases,whereas only 13% of mesothelioma cases stained positively to GlcNAc incontrast to 73% of metastatic adenocarcinoma cases. About 80% of themesothelioma cases showed binding capacities to TNF-alpha (45% ofmetastatic adenocarcinoma cases) and EGF (59% of metastaticadenocarcinoma cases). The ML-1-specific ligands could be detected in asimilar percentage (23-32%) in the different cohorts. Using antibodiesto certain carbohydrate-binding proteins, the expression of calcyclinwas relatively more abundant in the mesothelioma than in theadenocarcinoma cases. The heparin-specific lectin was seen mostfrequently in mesothelioma (40%) and only in 9% of metastaticadenocarcinoma. ML-1-specific ligands of intra-tumorous mononuclearinflammatory cells were present in 22/25 mesothelioma and in 9/10 ofadenocarcinoma with histochemically observed presence ofTNF-gamma-specific binding sites. Since non-specific immunostimulatorytherapy with mistletoe lectin has yielded antimetastatic effects in miceand is under investigation in clinical trials, it is noteworthy that theexpression of mistletoe-specific receptors of intra-tumorousinflammatory cells coincides with the presence of TNF-alpha-specificbinding sites of tumor cells.

Keyword(s): Medical:mesothelioma /diagnosis

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