de Sá Sandra Valéria, Corrêa-Giannella Maria Lúcia, Machado Márcio Carlos, de Souza Jean Jorge S, Pereira Maria Adelaide Albergaria, Patzina Rosely Antunes, Siqueira Sheila Aparecida Coelho, Machado Marcel Cerqueira César, Giannella-Neto Daniel
Laboratory for Cellular and Molecular Endocrinology (LIM-25), University of São Paulo School of Medicine, São Paulo, Brazil.
Endocr Relat Cancer. 2006 Mar;13(1):69-78. doi: 10.1677/erc.1.00962.
Insulinomas are rare endocrine neoplasias that constitute the most frequent islet cell tumours. Somatostatin (SST) analogs are tentatively used to inhibit insulin secretion and control tumour growth in patients with local invasion or inoperative metastasis, but variable responses have been reported. Data regarding somatostatin receptor (SSTR) subtypes expression in insulinomas are conflicting. In this study, we evaluated 16 cases of primary insulinomas (including four primary plurihormonal tumours) and two hepatic metastases. Histopathological and immunohistochemical analysis for some features associated with tumour aggressiveness and semi-quantitative RT-PCR for SSTR1-5 and real-time qPCR for SSTR5 were performed. SSTR subtypes 1, 3, and 5 were expressed in 100%, SSTR2 in 89%, and SSTR4 only in 22% of the insulinomas. SSTR5 mRNA was positively correlated with histopathological features related to tumour aggressiveness (large tumour diameter, well-differentiated endocrine tumour with uncertain behaviour and higher number of cells with nuclear atypia). SSTR5 mRNA expression in primary insulinomas was lower than in primary plurihormonal tumours (P < 0.05). The observed positive correlation between SSTR5 expression and tumour size suggests that the use of SST analogues more specific to SSTR5 in the treatment of insulinomas deserves attention.
胰岛素瘤是罕见的内分泌肿瘤,是最常见的胰岛细胞瘤。生长抑素(SST)类似物被尝试用于抑制胰岛素分泌,并控制局部侵袭或无法手术切除的转移患者的肿瘤生长,但报道的反应不一。关于胰岛素瘤中生长抑素受体(SSTR)亚型表达的数据存在矛盾。在本研究中,我们评估了16例原发性胰岛素瘤(包括4例原发性多激素肿瘤)和2例肝转移瘤。对与肿瘤侵袭性相关的一些特征进行了组织病理学和免疫组织化学分析,并对SSTR1 - 5进行了半定量逆转录聚合酶链反应(RT-PCR),对SSTR5进行了实时定量聚合酶链反应(qPCR)。胰岛素瘤中SSTR亚型1、3和5的表达率为100%,SSTR2为89%,SSTR4仅为22%。SSTR5 mRNA与肿瘤侵袭性相关的组织病理学特征(肿瘤直径大、行为不确定的高分化内分泌肿瘤以及核异型性细胞数量较多)呈正相关。原发性胰岛素瘤中SSTR5 mRNA的表达低于原发性多激素肿瘤(P < 0.05)。观察到的SSTR5表达与肿瘤大小之间的正相关表明,在胰岛素瘤治疗中使用对SSTR5更具特异性的SST类似物值得关注。