Faculdade de Medicina, Universidade de São Paulo, Unidade de Suprarrenal, Brazil.
Clinics (Sao Paulo). 2012;67(2):95-8. doi: 10.6061/clinics/2012(02)02.
Endostatin is a potent endogenous inhibitor of angiogenesis. It is derived from the proteolytic cleavage of collagen XVIII, which is encoded by the COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism p.D104N impairs the activity of endostatin, resulting in a decreased ability to inhibit angiogenesis. This polymorphism has been previously analyzed in many types of cancer and has been considered a phenotype modulator in some benign and malignant tumors. However, these data are controversial, and different results have been reported for the same tumor types, such as prostate and breast cancer. The purpose of this study was to genotype the p.D104N variant in a cohort of pediatric and adult patients with adrenocortical tumors and to determine its possible association with the biological behavior of adrenocortical tumors.
DNA samples were obtained from 38 pediatric and 56 adult patients (0.6-75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or fresh frozen tissue samples were unavailable. Restriction fragment length polymorphism analysis was used to genotype the patients and 150 controls. The potential associations of the p.D104N polymorphism with clinical and histopathological features and oncologic outcome (age of onset, tumor size, malignant tumor behavior, and clinical syndrome) were analyzed.
Both the patient group and the control group were in Hardy-Weinberg equilibrium. The frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD), 15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3% and 2.0%, respectively. We did not observe any association of this variant with clinical or histopathological features or oncologic outcome in our cohort of pediatric and adult patients with adrenocortical tumors.
血管内皮抑素是一种有效的内源性血管生成抑制剂。它来源于胶原 XVIII 的蛋白水解裂解，而胶原 XVIII 由 COL18A1 基因编码。一个编码功能多态性 p.D104N 的多态性 COL18A1 等位基因削弱了血管内皮抑素的活性，导致其抑制血管生成的能力降低。这种多态性以前在许多类型的癌症中进行过分析，并被认为是一些良性和恶性肿瘤的表型调节剂。然而，这些数据存在争议，并且对于同一肿瘤类型，如前列腺癌和乳腺癌，已经报道了不同的结果。本研究的目的是对一组儿童和成人肾上腺皮质肿瘤患者的 p.D104N 变体进行基因分型，并确定其与肾上腺皮质肿瘤生物学行为的可能关联。
从 38 名儿童和 56 名成人（0.6-75 岁）肾上腺皮质肿瘤患者中获得 DNA 样本。当无法获得血液样本或新鲜冷冻组织样本时，从外周血、冷冻组织或石蜡包埋的肿瘤块中获得 DNA 样本。使用限制性片段长度多态性分析对患者和 150 名对照进行基因分型。分析 p.D104N 多态性与临床和组织病理学特征以及肿瘤学结果（发病年龄、肿瘤大小、恶性肿瘤行为和临床综合征）的潜在关联。
患者组和对照组均处于哈迪-温伯格平衡。患者组 p.D104N 多态性的频率为 81.9%（DD）、15.9%（DN）和 2.2%（NN）。在对照组中，这些频率分别为 80.6%、17.3%和 2.0%。在我们的儿童和成人肾上腺皮质肿瘤患者队列中，我们没有观察到该变体与临床或组织病理学特征或肿瘤学结果之间存在任何关联。
