Delou João Marcos de Azevedo, Vignal Giselle Maria, Índio-do-Brasil Vanessa, Accioly Maria Theresa de Souza, da Silva Taiana Sousa Lopes, Piranda Diogo Nascimento, Sobral-Leite Marcelo, de Carvalho Marcelo Alex, Capella Márcia Alves Marques, Vianna-Jorge Rosane
Programa de Bioquímica e Biologia Celular, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro.
Programa de Farmacologia, Coordenação de Pesquisa, Instituto Nacional de Câncer.
Breast Cancer (Dove Med Press). 2017 Jun 10;9:415-428. doi: 10.2147/BCTT.S131284. eCollection 2017.
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, 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 in breast tumors as a function of genetic, clinical, and histopathological variables. The 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 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 [OR] =0.24; 95% confidence interval [CI] =0.13-0.45), lymph node status < pN2 (OR =0.27; 95% CI =0.10-0.71), tumor size >2 cm (OR =0.55; 95% CI =0.32-0.93), and hypertensive status (OR =0.42; 95% CI =0.24-0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients ( log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21-9.91) or for those with triple-negative tumors ( log-rank =0.007; HR =11.41; 95% CI =1.29-100.67). The loss of constitutive expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.
基因编码一种三磷酸腺苷结合盒转运蛋白，它不仅赋予恶性细胞多药耐药表型，还存在于多种非恶性组织中。在过去三十年里，许多作者都描述了其在乳腺癌中的表达情况，但各研究中的表达程度有所不同，对于其在致癌过程或肿瘤对抗肿瘤药物反应中的潜在作用也没有达成共识。本研究旨在根据基因、临床和组织病理学变量来描述其在乳腺肿瘤中的表达特征。还在肿瘤旁的非恶性乳腺组织和良性病变中评估了其表达情况。通过免疫组织化学对从巴西乳腺癌女性前瞻性队列中获取的切除乳房组织标本进行ABCB1蛋白检测。还评估了ABCB1蛋白水平与mRNA、基因多态性以及临床和组织病理学变量之间的关联。进行了Kaplan-Meier曲线分析和多变量Cox回归分析，以确定乳腺癌患者无病生存的独立预测因素。在86.3%（656例）的乳腺肿瘤、98.8%（606例）的肿瘤旁非恶性乳腺组织和100%（28例）的良性病变中检测到了ABCB1。乳腺肿瘤中ABCB1蛋白水平降低与三阴性亚型（调整后的优势比[OR]=0.24；95%置信区间[CI]=0.13 - 0.45）、淋巴结状态<pN2（OR =0.27；95% CI =0.10 - 0.71）、肿瘤大小>2 cm（OR =0.55；95% CI =0.32 - 0.93）以及高血压状态（OR =0.42；95% CI =0.24 - 0.73）相关，并且与所有乳腺癌患者（对数秩检验=0.012；风险比[HR]=3.46；95% CI =1.21 - 9.91）或三阴性肿瘤患者（对数秩检验=0.007；HR =11.41；95% CI =1.29 - 100.67）的无病生存期缩短显著相关。乳腺癌中组成型表达的缺失，尤其是在三阴性肿瘤中，似乎表明预后较差的一个亚组。
