concanavalin-a and Carcinoid-Tumor

This study analyzed the structural differences of the carbohydrate chains of circulating free alpha-submit (alpha-SU) hypersecreted in various non-tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH-, GH- and pure alpha-secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free alpha-SU were investigated by means of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free alpha-SU in three different fractions (unbound = UB, weakly bound = WB and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of alpha-SU in serum and in Con-A fractions were measured by a sensitive and specific IRMA. Free alpha-SU hypersecreted from postmenopausal women, primary hypothyroids, and patients with chronic uremia showed similar binding patterns to Con-A, the percentage of UB fractions (UB: 44.5 +/- 1.9%, 39.5 +/- 3.8%, 48.2 +/- 5.6% respectively) being higher than both WB and FB fractions (WB: 33.2 +/- 1.4%, 30.7 +/- 4.6%, 28.5 +/- 2.1%; FB: 22.3 +/- 0.7%, 29.8 +/- 6.6%, 23.3 +/- 4.2% respectively). In normal fetuses the amount of UB fraction was very high (UB: 70.7 +/- 5.4%). Free alpha-SU from patients with TSH- and GH-secreting adenomas showed a binding pattern to Con-A significantly different from that observed in postmenopausal women taken as controls, the WB fractions being significantly higher (WB: 56.9 +/- 16.8% and 71 +/- 12.4% respectively, P < 0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature alpha-SU molecules eluted in the FB fraction, was found in patients with pure alpha-secreting adenomas. This chromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoids (FB: 41.8 +/- 5.0%, 22.3 +/- 0.7%, 16.8 +/- 6.6%, 10.6 +/- 2.0% respectively). Moreover, in these latter patients the pattern of free alpha-SU binding was exactly the opposite of that observed in pure alpha-secreting adenomas, with a prevalence of mature alpha-SU molecules (UB: 59.1 +/- 4.4 vs 18.3 +/- 7.2%). In conclusion, our data on Con-A affinity chromatography clearly demonstrate that carbohydrate branching of circulating free alpha-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral conditions. Moreover, the finding of a greater prop

Topics: Adenoma; Adult; Carcinoid Tumor; Chromatography, Affinity; Concanavalin A; Fetus; Glycoconjugates; Glycoprotein Hormones, alpha Subunit; Humans; Hypothyroidism; Intestinal Neoplasms; Pituitary Neoplasms; Postmenopause; Protein Binding; Uremia

A 67-year-old man presented with a pulmonary atypical carcinoid tumor with marked elevation of the serum alpha-fetoprotein (AFP) level to 181,000 ng/ml and no hepatic metastases. Immunohistochemistry revealed AFP-positive fine granules, sparsely distributed in some cells. The proportion of the concanavalin A nonbinding subfraction was 33.7%. Light microscopy revealed hyaline globules within or outside the clear and reticular cytoplasm of a few cells. These were ultrastructurally electron-dense materials similar to the hyaline bodies observed in yolk sac tumors. The Grimelius silver method stained only a few cells and very few cells showed a positive Masson-Fontana reaction. Electron microscopy revealed secretory granules measuring 220 nm on the average in scattered cells. Immunohistochemical studies showed 5-hydroxytryptophan in many cells and 5-hydroxytriptamine or serotonin in only a few cells. As for polypeptide hormones, gastrin was detected and in autopsy specimens carcinoembryonic antigen (CEA) immunoreactive cells were observed. Past case reports on the coexistence of carcinoid tumors and adenocarcinomas in the digestive tract suggest that the tumor cells in our case are also derived from primitive or stem cells of endodermal origin and expressed unusual differentiation in the course of treatment.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoid Tumor; Concanavalin A; Cytoplasmic Granules; Humans; Immunoelectrophoresis, Two-Dimensional; Immunohistochemistry; Lung Neoplasms; Male; Microscopy, Electron