Abstract
Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3-6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antineoplastic Agents, Hormonal / therapeutic use
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Female
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Gene Expression
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Head and Neck Neoplasms / drug therapy
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Head and Neck Neoplasms / genetics*
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Head and Neck Neoplasms / secondary
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Lung Neoplasms / secondary
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Male
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Middle Aged
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Neoplasm Grading
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Neoplasm Recurrence, Local / drug therapy
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Neoplasm Recurrence, Local / genetics*
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Neoplasm Recurrence, Local / pathology
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Octreotide / therapeutic use
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Protein Isoforms / genetics
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RNA, Messenger / genetics*
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Receptors, Somatostatin / genetics*
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Thyroid Gland / drug effects
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Thyroid Gland / metabolism
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Thyroid Gland / pathology
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Thyroid Neoplasms / drug therapy
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Thyroid Neoplasms / genetics*
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Thyroid Neoplasms / pathology
Substances
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Antineoplastic Agents, Hormonal
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Protein Isoforms
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RNA, Messenger
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Receptors, Somatostatin
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somatostatin receptor 5
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Octreotide
Grants and funding
M. Puig-Domingo, J.P. Castaño, R.M. Luque and I. Halperin have received lectures fees from Novartis and Ipsen. M. Puig-Domingo has received honoraria for participation in Advisory boards from Genzyme. This work has been funded by the following grants: BIO-0139, CTS-5051, PI-036-2012, BFU2010-19300, CIBERobn, (to R.M. Luque and J.P. Castaño); “Sara Borrell” program CD11/00276 (to M.D. Gahete) and “Juan de la Cierva” program JCI-2009-05675 (to L.M. López-Sánchez). This work was partially supported by Novartis Oncology Spain (to M. Puig-Domingo and I. Halperin). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.