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肿瘤相关巨噬细胞与绝经后乳腺癌患者的他莫昔芬耐药相关。

Tumor-associated macrophages are correlated with tamoxifen resistance in the postmenopausal breast cancer patients.

作者信息

Xuan Qi-jia, Wang Jing-xuan, Nanding Abiyasi, Wang Zhi-peng, Liu Hang, Lian Xin, Zhang Qing-yuan

机构信息

Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, 150081, Heilongjiang, People's Republic of China.

出版信息

Pathol Oncol Res. 2014 Jul;20(3):619-24. doi: 10.1007/s12253-013-9740-z. Epub 2014 Jan 12.

Abstract

Tumor-associated macrophages (TAMs) have been correlated with increased angiogenesis and poor prognosis in breast cancer. However, the precise role of TAMs in tamoxifen resistance remains unclear. We used immunohistochemical method to examine the expression of epidermal growth factor receptor (EGFR) and CD163+ macrophages in 100 breast cancer tissues. The clinical and biological features of 100 patients were estrogen receptor (ER)-positive and human epidermal growth factor receptor 2(Her-2)-negative tumors. The tamoxifen resistant tissues (n = 48) were the surgical excision samples from patients who developed recurrence or metastasis at the time of adjuvant tamoxifen treatment. The tamoxifen resistant tissues were contrast to tamoxifen sensitive tissues (n = 52). Positive staining for EGFR and CD163+ macrophages were observed in 21 samples (43.8 %) and in 26 samples (54.2 %) respectively in tamoxifen resistance group, which were higher than that of tamoxifen sensitive group (P = 0.001 and P = 0.000279 respectively). Significant positive correlations were found between the expression of EGFR and CD163+ macrophages (r = 0.567, P < 0.01). CD163+ macrophages were positively correlated with tumor size, lymph node metastasis and obesity. Obesity was also related to tamoxifen resistance (P < 0.05). The patients with higher density of CD163+ macrophages infiltration suffered from shorter time to develop recurrence or metastasis (P < 0.05). TAMs may be associated with tamoxifen resistance. Further studies are needed to investigate the potential mechanism between TAMs and tamoxifen resistance.

摘要

肿瘤相关巨噬细胞(TAMs)与乳腺癌中血管生成增加及预后不良相关。然而,TAMs在他莫昔芬耐药中的确切作用仍不清楚。我们采用免疫组化方法检测了100例乳腺癌组织中表皮生长因子受体(EGFR)和CD163+巨噬细胞的表达。100例患者的临床和生物学特征为雌激素受体(ER)阳性且人表皮生长因子受体2(Her-2)阴性肿瘤。他莫昔芬耐药组织(n = 48)为辅助他莫昔芬治疗时出现复发或转移患者的手术切除样本。将他莫昔芬耐药组织与他莫昔芬敏感组织(n = 52)进行对比。在他莫昔芬耐药组中,分别有21个样本(43.8%)和26个样本(54.2%)观察到EGFR和CD163+巨噬细胞呈阳性染色,高于他莫昔芬敏感组(分别为P = 0.001和P = 0.000279)。EGFR表达与CD163+巨噬细胞之间存在显著正相关(r = 0.567,P < 0.01)。CD163+巨噬细胞与肿瘤大小、淋巴结转移和肥胖呈正相关。肥胖也与他莫昔芬耐药相关(P < 0.05)。CD163+巨噬细胞浸润密度较高的患者复发或转移发生时间较短(P < 0.05)。TAMs可能与他莫昔芬耐药有关。需要进一步研究来探讨TAMs与他莫昔芬耐药之间的潜在机制。

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