Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors. Endocr. Relat. Cancer. 14, 221-232

Uppsala University, Uppsala, Uppsala, Sweden
Endocrine Related Cancer (Impact Factor: 4.81). 07/2007; 14(2). DOI: 10.1677/ERC-06-0074


Neuroendocrine tumors (NETs) of the digestive tract are a heterogeneous group of rare malignancies. Three major subgroups can be defined: pancreatic endocrine tumors, carcinoid tumors, and poorly differentiated gastroenteropancreatic NETs. Classically, digestive NETS have been considered to have an indolent course characterized for prolonged stabilizations or slow progressions, but there are clear differences in terms of aggressiveness, clinical course, and response to treatment among them. Retrospective studies have identified several clinicopathological and immunohistochemical factors as angioinvasion and proliferative index assessed by Ki-67 expression, which predict biological behavior and correlate with survival. Chemotherapy regimens based on the combination of several active drugs such as streptozocin, doxorubicin, 5-fluorouracil, dacarbazine, and temozolomide show low response rates, which sets the need to improve the results of the medical treatment of these malignancies. This review will analyze the role of Ki-67 in digestive NETs under a clinical perspective and will suggest future fields for development of this approach that enable a better patient selection for chemotherapy. Also a comprehensive review of the literature about chemotherapy in NETs is presented.

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    • "Neuroendocrine cells are located diffusely throughout the human body and are found in the gastrointestinal tract, pancreas, lung, thyroid, adrenal, and many other organs. Although the gastrointestinal tract has the largest proportion of neuroendocrine cells, neuroendocrine tumors (NETs) account for only 2% of all gastrointestinal malignancies [1]. These tumors are a heterogeneous group of neoplasms composed of cells containing neuroendocrine secretory granules in the cytoplasm which can be identified ultrastructurally. "
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    • "In addition, trichrome staining revealed that the stroma was similarly abundant in the tumors of both groups of mice (Fig. 1C). By contrast, Ki67 and CD34, which are markers for proliferation and angiogenesis, respectively (Le Mercier et al 2009, Vilar et al 2007), were markedly decreased in tumors from GPC1 -/-by comparison with GPC +/+ mice (Fig. 2). Immunofluorescent staining for Ki67 indicated that proliferation was significantly reduced in both the PanIN (CK19-positive) and stromal cells of tumors from 65 day old GPC1 -/-transgenic mice (Fig. 3). "
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