An immunohistochemical investigation of the expression of somatostatin receptor subtypes - should therapeutic trials be performed to determine the efficacy of somatostatin analogs in treating advanced thyroid malignances?

Abstract

Somatostatin and its analogs through the specific receptor are known to demonstrate antiproliferative, anti-angiogenic and pro-apoptotic actions. The presence of SSTR-1-5 has not been sufficiently explored in poorly differentiated and undifferentiated thyroid tumors. The aim was to investigate the SSTR subtypes expression in these aggressive thyroid tumors. The study also discusses the usefulness of SSTR analogs as an alternative to conventional forms of therapy.

METHODS: The analysis was performed by immunohistochemistry on the 14 archived poorly differentiated and 4 anaplastic thyroid carcinomas. A group of benign thyroid pathologies consisting of 11 patients was also included.

RESULTS: SSTR-1, 2A, 2B, 3 and 5 were found to be expressed both in benign and malignant thyroid diseases, while SSTR-4 was not. Expression of SSTR-1 and SSTR-5 was found in samples with poorly differentiated thyroid tumors with a score of at least 2.0 being recorded in 10 tumors (71.4%). For SSTR-2A the same or higher score was noted in 5/14 (35.7%), for SSTR-2B in 4/14 (28.6%) and for SSTR-3 in 3/14 (21.4%) samples. SSTR-1, 2B and 5 were found to have a score of at least 2.0 in all undifferentiated thyroid tumors. Immunostaining of SSTR-2A and 3 was observed in 50% of samples. The immunopositive reactions were observed both in the membranes and cytoplasm of the thyroid cancer' cells. In some cases positive immunostaining was localized also in the endothelium of intrathyroidal blood vessels.

CONCLUSIONS: The somatostatin multiligand analogs or selective agonists could be considered alternatives to conventional therapeutic agents in aggressive thyroid tumors.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide.