The truncated isoform of somatostatin receptor5 (sst5TMD4) is associated with poorly differentiated thyroid cancer.
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.
Service of Endocrinology and Nutrition, Department of Medicine, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.
Manel
M
Puig-Domingo
Department of Cell Biology, Physiology and Immunology University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
Raúl M
RM
Luque
Service of Endocrinology and Nutrition, Department of Medicine, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.
Jordi L
JL
Reverter
Department of Cell Biology, Physiology and Immunology University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
Laura M
LM
López-Sánchez
Department of Cell Biology, Physiology and Immunology University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
Manuel D
MD
Gahete
IPSEN, Milford, Massachusetts, United States of America.
Michael D
MD
Culler
Service of Endocrinology, Hospital Clínico de Valladolid, Valladolid, IEN-UVa, Valladolid, Spain.
Gonzalo
G
Díaz-Soto
Service of Nuclear Medicine, Hospital Clínic de Barcelona, Barcelona, Spain.
Francisco
F
Lomeña
Service of Radiology, Hospital Clínic de Barcelona, Barcelona, Spain.
Mattia
M
Squarcia
Department of Pathology, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.
José Luis
JL
Mate
Service of Endocrinology and Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain.
Mireia
M
Mora
Service of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain.
Laureano
L
Fernández-Cruz
Service of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain.
Oscar
O
Vidal
Service of General Surgery, Department of Surgery, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.
Antonio
A
Alastrué
Service of General Surgery, Department of Surgery, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain ; Service of General Surgery, Department of Surgery, Vall d'Hebron Research Institute and Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Jose
J
Balibrea
Service of Endocrinology and Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain.
Irene
I
Halperin
Service of Endocrinology and Nutrition, Department of Medicine, Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.
Dídac
D
Mauricio
Department of Cell Biology, Physiology and Immunology University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
Justo P
JP
Castaño
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015282:Octreotide / Q000627:therapeutic use; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000235:genetics*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D020033:Protein Isoforms; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; D015282:Octreotide