Expression distribution of cancer stem cells, epithelial to mesenchymal transition, and telomerase activity in breast cancer and their association with clinicopathologic characteristics.

Expression distribution of cancer stem cells, epithelial to mesenchymal transition, and telomerase activity in breast cancer and their association with clinicopathologic characteristics.
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DOI:
10.4137/cpath.s19615
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发表时间:
2015
期刊:
Clinical medicine insights. Pathology
影响因子:
--
通讯作者:
John DV
John DV
中科院分区:
其他
文献类型:
--
作者:
Makki J;Myint O;Wynn AA;Samsudin AT;John DV

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共167例手术切除的原发性浸润性乳腺癌和63例转移性淋巴结病变,在福尔马林固定、石蜡包埋的组织中,通过免疫组化(IHC)双染IHC技术分析了CD44+CD24−低水平乳腺癌干细胞(CSC)标志物、上皮向间质转化(EMT)标志物和端粒酶活性的免疫组化(IHC)定位,通过双染色免疫荧光和流式细胞术技术验证结果。结果显示,具有CD44+CD24−low表型的CSC在淋巴结阳性肿瘤、高级别肿瘤和导管原位癌(DCIS)中显著增加。淋巴结转移灶端粒酶阳性率高。在转移性淋巴结病变和三阴性肿瘤中,EMT表达的肿瘤细胞数量相当高。EMT现象的发生通常伴随着CD44+CD24−low表型的CSC的共存。肿瘤细胞端粒酶活性的检测与肿瘤干细胞的存在无关。DCIS病变中CD44+CD24−low表型的CSC和经历EMT的细胞数量的增加可能是乳腺癌间质浸润和增殖的初始步骤,乳腺肿瘤中EMT的发生与CSC的高患病率相关,促进肿瘤的侵袭和转移。
A total of 167 surgically resected primary invasive breast carcinomas and 63 metastatic lymph node lesions were analyzed for immunohistochemical (IHC) localization of the CD44+CD24−low breast cancer stem cell (CSC) markers, epithelial to mesenchymal transition (EMT) markers, and telomerase activity by double-staining IHC technique, in formalin-fixed, paraffin-embedded tissue, the results were validated by double-staining immunofluorescent and flow cytometry techniques. The results showed that CSCs with CD44+CD24−low phenotype were significantly increased in node-positive tumors, high-grade tumors, and ductal carcinoma in situ (DCIS). There was a high incidence of telomerase expression in metastatic lymph node lesion. There were considerably high number of tumor cells with EMT expression in metastatic lymph node lesion, and triple-negative tumor. The occurrence of EMT phenomena was usually accompanied by the co-existence of CSCs of CD44+CD24−low phenotype. There was no association between the existence of CSCs and detection of telomerase activity in tumor cells. Increased numbers of both CSCs of CD44+CD24−low phenotype and cells underwent EMT in DCIS lesion might be an initial step in the stromal invasion and propagation of breast cancer, and occurrence of EMT in the breast tumor associated with high prevalence of CSCs, promoting tumor invasiveness and metastasis.