Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer.
Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer.
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DOI：
10.1158/1078-0432.ccr-09-1532
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发表时间：
2010-02-01
期刊：
影响因子：
--
通讯作者：
Polyak K
中科院分区：
文献类型：
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作者：
Park SY;Lee HE;Li H;Shipitsin M;Gelman R;Polyak K
目的探讨干细胞相关标志物在不同亚型、不同组织学分期乳腺肿瘤细胞水平上的表达。我们对12种蛋白[CD44、CD24、ALDH1、vimentin、osteonectin、EPCR、caveolin 1、connecnexin 43、cytokeratin 18 （CK18）、MUC1、claudin 7、GATA3]进行免疫组化分析，选取这些蛋白在47例浸润性导管癌（IDC）、135例浸润性导管原位癌（DCIS）、35例浸润性导管原位癌（DCIS）、58例单纯DCIS中分化程度较高、具有干细胞样特征的乳腺癌细胞中的差异表达。我们还分析了73例伴有相邻DCIS的idc，以确定个体肿瘤中组织学标记物表达的差异。双免疫组化检测CD44+/CD24 -和CD44 - /CD24+细胞。CD44和EPCR的表达在4个组织学组之间存在差异，侵袭性肿瘤的表达低于原位肿瘤，尤其是腔内A亚型。vimentin、osteonectin、connexin43、ALDH1、CK18、GATA3、MUC1的表达在某些组织学组中因肿瘤亚型而异。ALDH1阳性细胞在基底样和HER2+肿瘤中比在管腔肿瘤中更常见。在所有肿瘤中，69%的肿瘤检测到CD44+/CD24−细胞，100%的基底样肿瘤和52%的HER2+肿瘤含有这些细胞。我们的研究结果表明，在乳腺癌中，肿瘤细胞干细胞样和分化程度更高的细胞标记阳性的频率根据肿瘤亚型和组织学分期而变化。
To evaluate the expression of stem cell-related markers at the cellular level in human breast tumors of different subtypes and histologic stage. We performed immunohistochemical analyses of 12 proteins [CD44, CD24, ALDH1, vimentin, osteonectin, EPCR, caveolin 1, connexin 43, cytokeratin 18 (CK18), MUC1, claudin 7, and GATA3] selected based on their differential expression in breast cancer cells with more differentiated and stem cell-like characteristics in 47 cases of invasive ductal carcinoma (IDC) only, 135 cases of IDC with ductal carcinoma in situ (DCIS), 35 cases of DCIS with microinvasion, and 58 cases of pure DCIS. We also analyzed 73 IDCs with adjacent DCIS to determine the differences in the expression of markers by histology within individual tumors. CD44+/CD24− and CD44−/CD24+ cells were detected using double immunohistochemistry. CD44 and EPCR expression was different among the four histologic groups and was lower in invasive compared to in situ tumors, especially in luminal A subtype. The expression of vimentin, osteonectin, connexin 43, ALDH1, CK18, GATA3, and MUC1 differed by tumor subtype in some histologic groups. ALDH1 positive cells were more frequent in basal-like and HER2+ than in luminal tumors. CD44+/CD24− cells were detected in 69 % of all tumors with 100% of the basal-like and 52% of HER2+ tumors having some of these cells. Our findings suggest that in breast cancer the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage.