Endocrinology Department, Universidade Federal do Rio de Janeiro, R. Prof. Rodolpho Paulo Rocco, 255 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-913, Brazil.
Pathology department, Instituto Nacional do Cancer do Rio de Janeiro, R. Cordeiro da Graça, 156 - Santo Cristo, Rio de Janeiro, RJ, 20220-400, Brazil.
Endocrine. 2017 Dec;58(3):474-480. doi: 10.1007/s12020-017-1424-0. Epub 2017 Sep 25.
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.
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.
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).
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.
甲状腺髓样癌（MTC）是滤泡旁细胞的恶性肿瘤。由于它是一种神经内分泌肿瘤，因此已知其存在生长抑素受体（SSTRs）。迄今为止，尚未完全阐明 SSTR 亚型的实际频率及其对 MTC 细胞增殖的潜在影响（通过与内源性生长抑素结合）。本研究评估了 SSTR 亚型 1、2、3 和 5 的发生情况，以及每种亚型在 MTC 患者临床演变中可能发挥的作用。
这是一项回顾性纵向研究，分析了 42 例 MTC 甲状腺手术标本。使用针对 SSTR 亚型 1、2、3 和 5 的单克隆抗体进行免疫组织化学染色。根据每种 SSTR 亚型，将组织学材料分类为阴性、局灶性阳性或弥漫性阳性。评估了初始治疗反应、临床过程和患者死亡率，并与 SSTR 亚型的存在相关。
最常见的 SSTR 亚型是 SSTR 3，在考虑任何阳性模式时，81%的患者存在该亚型。然而，亚型 2 的阳性患者数量最少，只有 28.6%的患者存在任何阳性模式。亚型 1 和 5 的阳性率居中，其中亚型 1在 45.2%的患者中阳性，亚型 5在 54.8%的患者中阳性，在考虑任何阳性模式时。弥漫性阳性的 SSTR 1 的存在独立预测初始治疗的反应更好，风险比（HR）为 4.80（p=0.03）。
这是第一项显示 SSTR1 存在（通过单克隆免疫组织化学技术检测）与 MTC 患者初始治疗反应更好和可能长期临床反应更好相关的研究。此外，这些患者的 SSTR2 阳性率较低，这可能解释了诊断的低敏感性和基于奥曲肽的放射性同位素治疗反应有限。
