Lacombe Amanda Meneses Ferreira, Soares Iberê Cauduro, Mariani Beatriz Marinho de Paula, Nishi Mirian Yumie, Bezerra-Neto João Evangelista, Charchar Helaine da Silva, Brondani Vania Balderrama, Tanno Fabio, Srougi Victor, Chambo José Luiz, Costa de Freitas Ricardo Miguel, Mendonca Berenice Bilharinho, Hoff Ana O, Almeida Madson Q, Weigand Isabel, Kroiss Matthias, Zerbini Maria Claudia Nogueira, Fragoso Maria Candida Barisson Villares
Unidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, São Paulo, SP 05403-900, Brazil.
Serviço de Anatomia Patológica, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, São Paulo, SP 01246-000, Brazil.
Cancers (Basel). 2020 Jan 19;12(1):247. doi: 10.3390/cancers12010247.
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score ≥ 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0-4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score ≤ 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion ( = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 ( = 0.011)] and a high Ki67 index ( = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26-3.66; = 0.005) in all patients ( = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; = 0.027) in patients with localized disease at diagnosis ( = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.
肾上腺皮质癌（ACC）是一种罕见的内分泌恶性肿瘤，预后不良。尽管大多数患者预后不佳，但治疗策略并未取得进展。因此，发现新的预后生物标志物具有极大的意义。固醇O-酰基转移酶1（SOAT1）参与胆固醇酯化和脂滴形成。最近有研究表明，SOAT1抑制会导致ACC中的类固醇生成受损和细胞活力下降。迄今为止，尚无研究探讨SOAT1表达对ACC预后和临床结局的影响。我们通过定量实时聚合酶链反应和免疫组织化学方法，对巴西一家三级中心治疗的112例成人ACC（Weiss评分≥3）组织芯片中的SOAT1表达进行了评估。两名独立病理学家通过半定量方法（0-4）评估免疫组织化学结果。我们旨在评估SOAT1表达与临床、生化和解剖病理参数、无复发生存期（RFS）、无进展生存期（PFS）和总生存期（OS）之间的相关性。在该队列中，SOAT1蛋白表达存在异质性，37.5%的ACC表现出强烈的SOAT1蛋白表达（评分>2），而62.5%表现出弱或无蛋白表达（评分≤2）。强烈的SOAT1蛋白表达与ACC中的高侵袭性特征相关，如肿瘤皮质醇分泌过多（P = 0.01）、疾病晚期[欧洲肾上腺肿瘤研究网络（ENSAT）分期系统3和4（P = 0.011）]以及高Ki67指数（P = 0.002）。在多变量分析中，强烈的SOAT1蛋白表达是所有患者（n = 112）OS降低的独立预测因素（风险比（HR）2.15，95%置信区间（CI）1.26-3.66；P = 0.005），以及诊断时为局限性疾病患者（n = 83）RFS降低的独立预测因素（HR 2.1，CI 95% 1.09-4.06；P = 0.027）。我们的研究结果表明，SOAT1蛋白表达在ACC中具有预后价值，并强化了将SOAT1作为ACC患者可能的治疗靶点进行研究的重要性。
