Expression of somatostatin receptor subtypes in human pituitary adenomas -- immunohistochemical studies

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Published on Monday, 14 March 2016

Abstract

BACKGROUND: The highly variable expression of SSTR subtypes in pituitary adenomas (PA) may partially explain why the subgroup of somatotropinomas or other adenomas do not respond to the therapeutic action of currently used long-acting somatostatin analogues like octreotide or lanreotide.

MATERIAL AND METHODS: Our study summarizes the data on expression of all somatostatin receptor subtypes (SSTR 1-5), extended for 2A and 2B SSTR isoforms, revealed by means of immunohistochemistry in dependence to different hormonal phenotype of the tumour.

RESULTS: The pattern of SSTR immunostaining (estimated according to the percentage frequency of appearance) was in acromegaly: SSTR 5 > SSTR 1 > SSTR 2A = SSTR 3 > SSTR 2B, in prolactinomas: SSTR 2B = SSTR 3 = SSTR 5 > SSTR 1 = SSTR 2A, in gonadotropinomas: SSTR 3 > SSTR 2B > SSTR 1 = SSTR 2A > SSTR 5, in corticotropinomas: SSTR 2A > SSTR 1 = SSTR 3 > SSTR 5 > SSTR 2B. In PA immunonegative for pituitary hormones, we noticed only a weak staining of all receptor subtypes including SSTR 4. In plurihormonal adenomas with positive GH phenotype the staining pattern was: SSTR 5 > SSTR 1 = SSTR 2B and in plurihormonal PA with negative GH phenotype: SSTR 1 = SSTR 5 > SSTR 2A = SSTR 2B = SSTR 3. In plurihormonal adenoma with ACTH immunopositivity, the staining pattern was: SSTR = SSTR 2A = SSTR 3 = SSTR 5. SSTR 1 and SSTR 5 were the most frequent subtypes of somatostatin receptor in plurihormonal adenomas without ACTH expression.

CONCLUSIONS: Human PA represents a group of tumours with a much more differentiated appearance of somatostatin receptor subtypes. It is very important to determine the SSTR profile individually for each tumour to make an appropriate decision as to therapeutic strategy choice. Apart from applying SSTR 2 and SSTR 5-preferring octreotide and lanreotide - newly synthesized multiligand analogues, such as SOM 230, KE 108, or other SST selective analogues, may represent a further useful approach for the treatment, especially in cases other than somatotropinoma or thyrotropinoma.

 



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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);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (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);


 


- 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;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- 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;

- 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;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response.