Loss of constitutive ABCB1 expression in breast cancer associated with worse prognosis.
Loss of constitutive ABCB1 expression in breast cancer associated with worse prognosis.
复制标题
DOI：
10.2147/bctt.s131284
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Vianna-Jorge R
中科院分区：
文献类型：
--
作者：
Delou JMA;Vignal GM;Índio-do-Brasil V;Accioly MTS;da Silva TSL;Piranda DN;Sobral-Leite M;de Carvalho MA;Capella MAM;Vianna-Jorge R
ABCB 1基因编码一种腺苷5′-三磷酸结合盒转运体，它不仅在恶性肿瘤细胞中具有多药耐药表型，而且在多种非恶性肿瘤组织中也存在。在过去的30年里，ABCB 1在乳腺癌中的表达已经被许多作者描述，但是表达的程度在研究中不同，并且关于其在致癌作用或肿瘤对化疗药物的反应中的潜在作用没有达成共识。本研究旨在描述乳腺肿瘤中ABCB 1的表达与遗传、临床和组织病理学变量的关系。ABCB 1的表达也被评估在非恶性乳腺组织中的肿瘤相邻和良性病变。ABCB 1蛋白的检测是通过免疫组织化学方法从巴西乳腺癌妇女的前瞻性队列中获得的切除乳房组织标本中进行的。还评估了ABCB 1蛋白水平与ABCB 1 mRNA、基因多态性以及临床和组织病理学变量的相关性。采用Kaplan-Meier曲线和多因素考克斯回归分析方法分析乳腺癌患者无病生存的独立预测因素。ABCB 1在86.3%（656）的乳腺肿瘤、98.8%（606）的癌旁非恶性乳腺组织和100%（28）的良性病变中表达。乳腺肿瘤中ABCB 1蛋白水平降低与三阴性亚型相关（校正比值比[ORadj] =0.24; 95%置信区间[CI] =0.13-0.45），淋巴结状态<pN 2（ORadj =0.27; 95% CI =0.10-0.71），肿瘤大小>2 cm（ORadj =0.55; 95%CI =0.32-0.93），和高血压状态（ORadj =0.42; 95%CI =0.24-0.73），并且与所有乳腺癌患者的无病生存期缩短显著相关，（p对数秩=0.012;风险比[HR] =3.46; 95% CI =1.21-9.91）或三阴性肿瘤患者（p对数秩=0.007; HR =11.41; 95% CI =1.29-100.67）。在乳腺癌中，尤其是在三阴性肿瘤中，组成性ABCB 1表达的缺失似乎表明预后较差的亚组。
ABCB1 gene encodes an adenosine 5′-triphosphate–binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables. The ABCB1 expression was also evaluated in nonmalignant mammary tissues adjacent to tumors and in benign lesions. The detection of ABCB1 protein was performed by immunohistochemistry in tissue specimens of excised breasts obtained from a prospective cohort of Brazilian women with breast cancer. The association of ABCB1 protein levels with ABCB1 mRNA, gene polymorphisms, and clinical and histopathological variables was also evaluated. The Kaplan–Meier curves and multivariate Cox regression analyses were conducted to identify independent predictors of disease-free survival of patients with breast cancer. ABCB1 was detected in 86.3% (656) of breast tumors, 98.8% (606) of nonmalignant mammary tissue adjacent to tumors, and 100% (28) of benign lesions. Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [ORadj] =0.24; 95% confidence interval [CI] =0.13–0.45), lymph node status < pN2 (ORadj =0.27; 95% CI =0.10–0.71), tumor size >2 cm (ORadj =0.55; 95% CI =0.32–0.93), and hypertensive status (ORadj =0.42; 95% CI =0.24–0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (p log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21–9.91) or for those with triple-negative tumors (p log-rank =0.007; HR =11.41; 95% CI =1.29–100.67). The loss of constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.