Daniel Barretto Kendler1, Mario Lucio Araújo2, Renata Alencar3, Maria Theresa de Souza Accioly2, Daniel Alves Bulzico3, Cencita Cordeiro de Noronha Pessoa3, Fernanda Andrade Accioly3, Terence Pires de Farias4, Flaia Paiva Proença Lobo Lopes5, Rossana Corbo3, Mario Vaisman1, Fernanda Vaisman6. 1. Endocrinology Department, Universidade Federal do Rio de Janeiro, R. Prof. Rodolpho Paulo Rocco, 255 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-913, Brazil. 2. Pathology department, Instituto Nacional do Cancer do Rio de Janeiro, R. Cordeiro da Graça, 156 - Santo Cristo, Rio de Janeiro, RJ, 20220-400, Brazil. 3. Endocrinology Department, Instituto Nacional do Cancer do Rio de Janeiro, Praça da Cruz Vermelha 23, 8th floor, Centro, Rio de Janeiro, RJ, 20230-130, Brazil. 4. Head and Neck Surgery Department, Instituto Nacional do Cancer do Rio de Janeiro, Praça da Cruz Vermelha 23, 8th floor, Centro, Rio de Janeiro, RJ, 20230-130, Brazil. 5. Nuclear Medicine Department, Instituto Nacional do Cancer do Rio de Janeiro, Praça da Cruz Vermelha 23, 8th floor, Centro, Rio de Janeiro, RJ, 20230-130, Brazil. 6. Endocrinology Department, Instituto Nacional do Cancer do Rio de Janeiro, Praça da Cruz Vermelha 23, 8th floor, Centro, Rio de Janeiro, RJ, 20230-130, Brazil. fevaisman@globo.com.
Abstract
PURPOSE: Medullary thyroid carcinoma (MTC) is a malignant neoplasm of parafollicular cells. Because it is a neuroendocrine tumor, it has known somatostatin receptors (SSTRs). The actual frequencies of the SSTR subtypes and their potential influences (by binding with endogenous somatostatin) on MTC cell proliferation have not been fully elucidated to date. The present study evaluated the occurrence of SSTR subtypes 1, 2, 3 and 5 as well as the possible role that each subtype plays in the clinical evolution of patients with MTC. METHODS: This retrospective, longitudinal study analyzed thyroid surgical material from 42 patients with MTC. Immunohistochemical staining was performed with monoclonal antibodies against subtypes 1, 2, 3 and 5 of SSTR. The histological material was classified as negative, focal positive or diffuse positive, in relation to each of the SSTR subtypes. The initial response to treatment, clinical course and patient mortality rate were assessed and related to the presence of SSTR subtypes. RESULTS: The most prevalent SSTR subtype was SSTR 3, which was found in 81% of the patients, when considering any pattern of positivity. However, subtype 2 had the lowest number of positive patients, with 28.6% demonstrating any positive pattern. Subtypes 1 and 5 had an intermediate prevalence of positivity, with subtype 1 present in 45.2% of the patients and subtype 5 positive in 54.8% of the patients, when considering any pattern of positivity. The presence of STR 1, in the form of diffuse positivity, independently predicted a better response to the initial therapy, with a hazard ratio (HR) of 4.80 (p = 0.03). CONCLUSION: This is the first study to show the correlation of the presence of SSTR1, detected by monoclonal immunohistochemical techniques, and better response to initial treatment and possibly better long-term clinical response in patients with MTC. In addition, these patients had low positivity rates for SSTR2, which might explain the low sensitivity of diagnostic and limited therapeutic response to octrotide based radioisotopes.
PURPOSE: Medullary thyroid carcinoma (MTC) is a malignant neoplasm of parafollicular cells. Because it is a neuroendocrine tumor, it has known somatostatin receptors (SSTRs). The actual frequencies of the SSTR subtypes and their potential influences (by binding with endogenous somatostatin) on MTC cell proliferation have not been fully elucidated to date. The present study evaluated the occurrence of SSTR subtypes 1, 2, 3 and 5 as well as the possible role that each subtype plays in the clinical evolution of patients with MTC. METHODS: This retrospective, longitudinal study analyzed thyroid surgical material from 42 patients with MTC. Immunohistochemical staining was performed with monoclonal antibodies against subtypes 1, 2, 3 and 5 of SSTR. The histological material was classified as negative, focal positive or diffuse positive, in relation to each of the SSTR subtypes. The initial response to treatment, clinical course and patient mortality rate were assessed and related to the presence of SSTR subtypes. RESULTS: The most prevalent SSTR subtype was SSTR 3, which was found in 81% of the patients, when considering any pattern of positivity. However, subtype 2 had the lowest number of positive patients, with 28.6% demonstrating any positive pattern. Subtypes 1 and 5 had an intermediate prevalence of positivity, with subtype 1 present in 45.2% of the patients and subtype 5 positive in 54.8% of the patients, when considering any pattern of positivity. The presence of STR 1, in the form of diffuse positivity, independently predicted a better response to the initial therapy, with a hazard ratio (HR) of 4.80 (p = 0.03). CONCLUSION: This is the first study to show the correlation of the presence of SSTR1, detected by monoclonal immunohistochemical techniques, and better response to initial treatment and possibly better long-term clinical response in patients with MTC. In addition, these patients had low positivity rates for SSTR2, which might explain the low sensitivity of diagnostic and limited therapeutic response to octrotide based radioisotopes.
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Authors: Lisa H de Vries; Lutske Lodewijk; Stefan M Willems; Koen M A Dreijerink; Bart de Keizer; Paul J van Diest; Abbey Schepers; Han J Bonenkamp; Ilse A C H van Engen-van Grunsven; Schelto Kruijff; Bettien M van Hemel; Thera P Links; Els J M Nieveen van Dijkum; Susanne van Eeden; Gerlof D Valk; Inne H M Borel Rinkes; Menno R Vriens Journal: Endocrine Date: 2018-08-20 Impact factor: 3.633