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凝集素组织化学显示SNA作为一种用于乳腺浸润性导管癌的预后碳水化合物依赖性探针:一种临床病理和免疫组化辅助工具。

Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool.

作者信息

dos-Santos Petra B, Zanetti Juliana S, Vieira-de-Mello Gabriela S, Rêgo Moacyr B M, Ribeiro-Silva A Alfredo, Beltrão Eduardo Isidoro Carneiro

机构信息

Keizo Asami Immunopathology Laboratory, Federal University of Pernambuco Recife, Pernambuco, 50670-901, Brazil.

Department of Pathology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, São Paulo, 14049-900, Brazil.

出版信息

Int J Clin Exp Pathol. 2014 Apr 15;7(5):2337-49. eCollection 2014.

Abstract

Increased sialylation and β1,6-branched oligosaccharides has been associated with a variety of structural changes in cell surface carbohydrates, most notably in tumorigenesis. Lectins are defined as proteins that preferentially recognize and bind carbohydrate complexes protruding from glycolipids and glycoproteins. This interaction with carbohydrates can be as specific as the interaction between antigen and antibody. Due to this type of interaction lectins have been used as experimental auxiliary tools in histopathological diagnosis of cancer. This study was designed to evaluate the differential expression of sialic acids and β1,6-N-acetylglucosaminyltransferase V (MGAT5) in invasive (IDC) and in situ (DCIS) ductal carcinoma of the breast and its possible application as prognostic biomarkers. A possible transition between pre-malign and malign lesions was evaluated using DCIS samples. Biopsies were analyzed regarding the expression of MUC1, p53, Ki-67, estrogen receptor, progesterone receptor, HER-2 and MGAT5. α2,6-linked sialic acids residues recognized by SNA lectin was overexpressed in 33.3% of IDC samples and it was related with Ki-67 (p=0.042), PR (p=0.029), lymphnodes status (p=0.017) and death (p=0.011). Regarding survival analysis SNA was the only lectin able to correlate with specific-disease survival and disease-free survival (p=0.024 and p=0.041, respectively), besides, it presents itself as an independent variable by Cox Regression analysis (p= 0.004). Comparing IDC and DCIS cases, only SNA showed different staining pattern (p=0.034). The presence of sialic acids on tumor cell surface can be an indicative of poor prognosis and our study provides further evidence that SNA lectin can be used as a prognostic probe in IDC and DCIS patients.

摘要

唾液酸化增加和β1,6-分支寡糖与细胞表面碳水化合物的多种结构变化有关,在肿瘤发生中尤为明显。凝集素被定义为优先识别并结合从糖脂和糖蛋白突出的碳水化合物复合物的蛋白质。这种与碳水化合物的相互作用可以像抗原与抗体之间的相互作用一样具有特异性。由于这种相互作用类型,凝集素已被用作癌症组织病理学诊断的实验辅助工具。本研究旨在评估唾液酸和β1,6-N-乙酰葡糖胺基转移酶V(MGAT5)在乳腺浸润性导管癌(IDC)和原位导管癌(DCIS)中的差异表达及其作为预后生物标志物的可能应用。使用DCIS样本评估了癌前病变和恶性病变之间的可能转变。对活检组织进行了MUC1、p53、Ki-67、雌激素受体、孕激素受体、HER-2和MGAT5表达的分析。SNA凝集素识别的α2,6-连接唾液酸残基在33.3%的IDC样本中过表达,并且与Ki-67(p=0.042)、PR(p=0.029)、淋巴结状态(p=0.017)和死亡(p=0.011)相关。关于生存分析,SNA是唯一能够与特定疾病生存率和无病生存率相关的凝集素(分别为p=0.024和p=0.041),此外,通过Cox回归分析它呈现为一个独立变量(p = 0.004)。比较IDC和DCIS病例,只有SNA显示出不同的染色模式(p=0.034)。肿瘤细胞表面唾液酸的存在可能预示预后不良,我们的研究提供了进一步的证据表明SNA凝集素可作为IDC和DCIS患者的预后探针。

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