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Myriem Boufraqech Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Lisa Zhang Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Meenu Jain Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Dhaval Patel Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Ryan Ellis Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Yin Xiong Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Mei He Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Naris Nilubol Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Maria J Merino Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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Electron Kebebew Endocrine Oncology Branch Laboratory of Pathology National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, Maryland 20892, USA

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The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-14-0077
Volume/Issue:
Volume 21: Issue 4
Free access
Maya B Lodish
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Karen T Adams Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Thanh T Huynh Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Tamara Prodanov Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Alex Ling Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Clara Chen Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Suzanne Shusterman Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Camilo Jimenez Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Maria Merino Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Marybeth Hughes Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Kendall W Cradic Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Dragana Milosevic Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Ravinder J Singh Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Constantine A Stratakis
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Karel Pacak Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney–Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection.

Article Type:
Research Article
DOI:
https://doi.org/10.1677/ERC-10-0004
Volume/Issue:
Volume 17: Issue 3
Free access