Pattern of endogenous lectins in a human epithelial tumor.

Salt and detergent extracts of a malignant epithelial tumor, obtained by extraction of acetone powder, were fractionated on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan, fucose, and heparin. Successive elution by chelating reagent and specific sugar resulted in isolation of different Ca2+-dependent and Ca2+-independent endogenous carbohydrate-binding proteins, as analyzed by gel electrophoresis. It appears from the analysis that certain bands represent newly identified proteins capable of binding to lactose (at Mr 64,000), melibiose (at Mr 28,000), and fucose (at Mr 62,000 and 70,000). Other carbohydrate-binding proteins isolated from this human tumor have been identified in normal, especially embryonic, tissues of different nonhuman vertebrates. The carbohydrate-binding proteins are assayable as agglutinin with rabbit erythrocytes and show no detectable enzymatic activity. They can thus be defined as lectins. The presence of a complex pattern of endogenous lectins and their biochemical characteristics may contribute to an understanding of intercellular interaction during the complex process of metastatic spread and may furthermore allow a new tool for diagnosis and a lectin-based therapy.

Pattern of endogenous lectins of a human sarcoma (Ewing's sarcoma) reveals differences to human normal tissues and tumors of epithelial and germ cell origin.

A human sarcoma, Ewing's sarcoma, contains activities of endogenous lectins. Fractionation of salt and detergent extracts by affinity chromatography on columns with immobilized sugars or glycoproteins results in the pattern of endogenous lectins for alpha- and beta-galactosides, alpha-mannosyl- and alpha-fucosyl-moieties. Whereas some lectins are known from normal, non-malignant human tissues or from a human epithelial tumor or a human germ cell tumor, a Ca2+-independent alpha- and beta-galactoside-binding protein at apparent molecular weight of 58 kilodaltons has so far not been characterized from any human source. The patterns for the tumors and human normal tissues reveal various differences in comparison between each other. These differences, documented for the first human sarcoma, human tumors of different histogenetic lineage and normal tissues are a first step to a lectin-based diagnosis and therapy of certain human cancer types.

Pancreatic polypeptide. A review.

Pancreatic polypeptide (PP), 36-amino acid peptide, may function as an important feedback inhibitor of pancreatic secretion after a meal. It arises from both islet and acinar cells of the pancreas. Release of PP by a meal, primarily protein, occurs in a biphasic manner. The first rapid release occurs as a result of vagal stimulation; the second, more prolonged rise (the so-called intestinal phase) occurs in response to hormonal stimulation, predominantly cholecystokinin. Plasma PP levels increase with age; PP levels are elevated above those of age-controlled normal subjects in diabetic patients and in some patients with pancreatic amine precursor uptake decarboxylase tumors. The value of plasma PP as a possible marker for pancreatic tumors is as yet unsettled but may be a valuable tool.

Chromogranin A, neuron-specific enolase and synaptophysin as neuroendocrine cell markers in the diagnosis of tumours of the gastro-entero-pancreatic system.

Neuroendocrine (NE) tumours of the gastro-entero-pancreatic tract were analysed immunohistochemically for the expression of chromogranin A, neuron-specific enolase and synaptophysin. In all cases at least one marker was present and in 17 out of 19 investigated neoplasms, at least one of the three markers could be demonstrated in more than 75% of the NE tumour cells. Monoclonal antibody chromogranin A stained a much higher proportion of NE cells in tumours with hormonal activity than in hormonally inactive ones. Immunostaining of the primary tumour as compared to its respective metastases was almost identical. Thus, chromogranin A, neuron-specific enolase and synaptophysin identify NE tumours and their metastases regardless of their localization and their state of hormonal activity. As 'panendocrine' markers of NE tumours they are of special diagnostic value in NE tumours that do not produce hormones and peptides.

Cytomorphology and marker expression of malignant neuroendocrine cells in pleural effusions.

Three cases of pulmonary neuroendocrine carcinoma with malignant pleural effusions were retrospectively studied to determine if cellular morphology and expression of neuroendocrine markers were the same in the fluid as in the solid milieu. In fluids, changes were noted in cell grouping, shape and cytoplasm. Neuroendocrine markers expressed in both solid and dispersed tumors were neuron-specific enolase (NSE) in all cases and leu-enkephalin in one case. Vasoactive intestinal polypeptide (two cases) and serotonin (one case) were detected only in the solid tumor. ACTH, bombesin and calcitonin were not expressed. We tentatively conclude that, in effusions, neoplastic neuroendocrine cells may alter their cytostructure, growth patterns and marker expression capabilities. NSE appears to be the most reliable neuroendocrine marker for use in small samples and with varying preparatory methods.

New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma.

The presence and distribution of cytokeratins, actin, neurofilament protein, neuron-specific enolase, S-100 protein, and different neuropeptides were studied immunohistochemically by the peroxidase-antiperoxidase immunoenzyme method or the avidin-biotin-peroxidase technique in 10 patients with primary cutaneous neuroendocrine carcinoma. In all cases of cutaneous neuroendocrine carcinoma, immunoreactivity for neuron-specific enolase, cytokeratin, and neurofilament was identified. No staining was found after incubation with antibodies to S-100 protein, actin, and other tested neuropeptides. The cytoplasmic cytokeratin and neurofilament immunoreactivity was particularly strong in perinuclear areas, sometimes showing an annular pattern or displaying a discoid profile. The diagnosis of cutaneous neuroendocrine carcinoma may be reliably made by the immunocytochemical demonstration of neuron-specific enolase and intermediate filaments (cytokeratin, neurofilament protein) by conventional microscopy. Cutaneous neuroendocrine carcinoma has morphological, immunological, and histogenetic similarities to carcinoid neoplasms of the gut. We favor the concept that cutaneous neuroendocrine carcinoma is derived from, or differentiates toward, dermal neuroendocrine cells.

[Immunocytochemistry of pancreatic and pancreatico-duodenal apudomas]. / Immunocytochimie des apudomes pancréatiques et pancréatico-duodénaux.

Immunocytochemical techniques, applied to material fixed with Bouin's fluid and using immune sera specific to various hormonal polypeptide(s), give a classification of pancreatic and pancreatico-duodenal apudomas based upon cellular functional activity. With a rane containing a minimum of five antibodies (gastrin, insulin, glucagon, somatostatin and pancreatic polypeptide), 15 tumours could be identified amongst the 22 tested. They were either "monohormonal" tumours (10 cases) or "bi- or polyhormonal" tumours (5 cases). In the remaining 7 cases, only rare cells were immunoreactive. A large number of immunoreactivities thus revealed in histological sections are clinically silent or are present in a "forme fruste".

Endocrine tumors of the pancreas.

The identification and description of a widely dispersed group of cells of common origin and biochemical characteristics, APUD cells, has allowed a better understanding and classification of endocrine tumors of the pancreas. Similarly, it has enabled the relationships between the endocrine tumors of the multiple endocrine neoplasia type I syndrome and the endocrine tumors of the pancreas to be better appreciated. This has facilitated both diagnosis and management of these conditions. The pluripotentiality of the cells of the APUD system combined with the certain existence of many unidentified peptides suggests the likelihood of other undescribed pancreatic endocrine tumors. Many of these are probably part of the heterogenous group of neoplasms currently designated as carcinoids, since their secretory products and exact cell types are not known. The recognition of the physiologic characteristics and cells of origin of these peptides, amines or other bioactive agents will allow delineation of the symptom complex and the identification of further functional tumors of the pancreas. The development of plasma radioimmunoassays for the various hormones and the appreciation of the specific clinical syndromes related to each tumor have enabled earlier diagnosis. The understanding of the hormonal physiopathologic functions has led to the evolution of specific therapeutic maneuvers. Provocative tests have allowed increased precision of the differential diagnosis, while selective arteriography and pancreatic venous sampling have greatly enhanced the accuracy of topical localization. The role of operation in tumor removal is still prominent, but malignant and recurrent tumors may now also be controlled with specific pharmacotherapy or appropriate endocrine cytotoxic agents. The use of peptides with antagonistic actions or the administration of specific antibodies to the active tumor products are areas of therapy that require further exploration.