Biological markers of neuroendocrine tumors of the gastrointestinal tract and pancreas. Clinical review

Based upon this cursory review of peptides and other substances which may act as markers for the presence of islet cell tumors or gastrointestinal carcinoids, certain themes seem to emerge. The first is that when these tumors are associated with endocrine syndromes, it is usually possible to attribute symptoms to the circulation of one dominant hormone. What is perhaps most remarkable is that one hormone can dominate the clinical picture, even if others are synthesized and secreted in excess. These tumors have clearly provided an opportunity to study mechanisms by which prohormones are synthesized and processed within secretory granules. A second theme is that many of these neoplasms express receptors for regulation of their secretory activities. Thus, most of the neuroendocrine tumors of the gut are responsive to secretory suppression by somatostatin. It is curious that a number of these lesions show a heightened responsiveness to certain secretagogues such as calcium ion and secretin. The explanation of such observations may lead to a greater understanding of the mechanisms, which regulate the response of the normal endocrine cell to secretory stimulation. A third theme is that a large number of specific peptides, amines, and enzymes can be detected in plasma samples or tissue preparations, which identify the neuroendocrine origin of these tumors. Nevertheless, few, if any, of these markers has as yet been shown to reliably distinguish the invasive or metastatic potential of such tumors. These observations might suggest that the machinery for synthesizing and secreting currently recognizable hormones has little to do with the properties which lead to cell proliferation, tumor invasiveness or potential for metastasis. If this were so, it is difficult to explain why some tumors secrete their hormone and prohormone products to such excess, and others do not. In this regard, the MEN syndromes may well provide the most intriguing models for studying the relationship of proliferation and neoplastic transformation of endocrine cells to synthesis and secretion of their hormone and monoamine products. The identification of specific growth factors in neuroendocrine tumors may be an important area for developing predictive indices of mitogenic rate, biosecretory activity, and angiogenic invasion.