BACKGROUND Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors. METHODS Twenty‐one formalin‐fixed, paraffin‐embedded specimens (15‐tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger—Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19. RESULTS Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %). CONCLUSIONS Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society.
Tankyrase, which functions at telomeres and other cellular compartments, is thought to be a positive regulator of telomerase; its isoenzyme tankyrase 2 has been cloned as a putative cancer antigen. This pilot immunohistochemical study was designed to examine whether tumors overexpress tankyrase 2. An antibody was generated by using synthetic peptide specific for tankyrase 2 and was tested by Western blot and immunocytochemically; no cross-reaction with isoenzyme 1 was revealed. Among tissue sections, two tumors of 18 specimens were positive for tankyrase 2. Others were negative or contained barely detectable protein. The surrounding normal tissues were negative. Tankyrase 2 was also revealed in epithelial cells of a limited number of normal renal tubules, whereas other renal tissues were negative. These data suggest that tankyrase 2 is not expressed ubiquitously in human tissues. To determine whether the up-regulation of tankyrase 2 is associated with tissue regeneration and cell proliferation, we compared the activity and concentration of the enzyme in a model human embryonic kidney cell line 293 arrested by serum deprivation and restimulated with serum. The serum-starved quiescent cell culture exhibited detectable protein as did the proliferating cells; enzyme activity dramatically increased in the latter. We conclude that pathologic overexpression of tankyrase 2 in some tumors may be a result of the cancer-related adaptation of the malignant cells dependent on tankyrase activity. Under normal conditions, the protein might be up-regulated during cell differentiation and also posttranslationally in proliferating cells.
Иммуногистохимическое определение экспрессии рецепторов к соматостатину 1, 2А, 3 и 5-го типов в нейроэндокринных опухолях различной локализации и степени злокачественности Актуальность. У пациентов с нейроэндокринными опухолями (НЭО) очень важно еще до начала лечения аналогами соматостатина прогнозировать его клинический эффект. Данных по иммуногистохимическому исследованию экспрессии рецепторов к соматостатину (ССР) разных типов, полученных на больших выборках НЭО различной локализации, функциональной активности и степени злокачественности, накоплено недостаточно, что и определило цель настоящего исследования. Материал и методы. Проводили иммуногистохимическое исследование с антителами к ССР 1, 2А, 3 и 5-го типов. Материалом исследования послужили тканевые образцы диагностических и операционных биопсий 399 НЭО: 168 поджелудочной железы, 120 желудочно-кишечного тракта (желудка -48, тонкой кишки -39, из которых опухолей двенадцатиперстной кишки -14, аппендикса -6, толстой и прямой кишки -15 и 12), 84 легких, 6 тимуса / средостения и 21 метастазов НЭО с неизвестной первичной локализацией. Результаты. Очень высокий уровень экспрессии ССР 2А, которые преимущественно связывают аналоги соматостатина, используемые сегодня в клинической практике, выявлен в НЭО Ключевые слова: рецепторы к соматостатину, нейроэндокринные опухоли, иммуногистохимия
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