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a Division of Endocrinology and Nephrology, University of Leipzig, Germany b Department of Surgery, University of Halle, Germany c National Institutes of Health, NINDS, Bethesda, Maryland, USA d Division of Hematology and Oncology, University of Leipzig, Germany e Department of Surgery, Sankt Georg Hospital, Leipzig, Germany f Department of Surgery II, University of Leipzig, Germany g Department of Nuclear Medicine, University of Leipzig, Germany h Division of Pediatric Hematology and Oncology, University of Leipzig, Germany i Ruhr University of Bochum, Bochum, Germany
Key Words: neuroendocrine • tumor • pheochromocytoma • imatinib • neurofibromatosis type 1
Address for correspondence: Christian A. Koch, M.D., F.A.C.P., F.A.C.E., Professor and Director, Division of Endocrinology, University of Mississippi, 2500 North State Street, Jackson, MS 39216. USA. Voice: 601-984-5525; fax: 601-984-5769. e-mail: ckoch{at}medicine.umsmed.edu
Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so-called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5-cm-large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.
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