Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers
Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers
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DOI：
10.1097/pat.0b013e3283534bcb
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发表时间：
2012-06-01
期刊：
影响因子：
4.5
通讯作者：
Gobbi, Helene
中科院分区：
文献类型：
--
作者：
De Brot, Marina;Rocha, Rafael M.;Gobbi, Helene
目的：我们评估了三阴性乳腺癌和基底样乳腺癌中癌症干细胞 (CSC) 相关标志物 ALDH1 和 EZH2 的表达，研究它们与临床病理特征和结果的关系。方法：从 140 例三阴性乳腺癌中获得临床病理数据。构建组织微阵列并对 ER、PR、HER2、ALDH1、EZH2、CK5、CK14、EGFR、p63、caveolin 和 p53 进行免疫组织化学分析。评估肿瘤细胞和基质中 ALDH1 的表达。进行多变量分析，包括所有显着变量。结果：大多数三阴性乳腺癌是无特殊类型（NST）的浸润性导管癌（116/140）。 140 例肿瘤细胞中，有 26 例肿瘤细胞胞质表达 ALDH1，而 140 例肿瘤细胞中有 117 例检测到基质表达。肿瘤细胞表达与任何参数均不相关。相反，基质表达与更好的总生存率相关（p=0.044）。 Cox 回归模型评估显示，当肿瘤间质中未发现 ALDH1 时，乳腺癌死亡的 HR 为 2.80（HR = 1/0.357 = 2.80；95%CI 0.178-0.714；p=0.004），与年龄、组织学类型/分级、淋巴结状态、分期、复发和基础标志物表达无关。在 140 例三阴性乳腺癌中，有 120 例发现 EZH2 高表达，并且与其他变量无关。基底样癌症占三阴性乳腺癌的 75% (105/140)。有趣的是，我们发现 EZH2 和 CK14 表达之间存在关联 (p=0.041)。结论：ALDH1 表达在三阴性乳腺癌的肿瘤相关基质细胞中很常见，并且与更好的预后相关。研究 CSC 对乳腺癌预后的影响时应考虑肿瘤微环境。
Aims: We assessed the expression of ALDH1 and EZH2, cancer stem cell (CSC) related markers, in triple negative and basal-like breast cancers, investigating their association with clinicopathological features and outcome.Methods: Clinicopathological data were obtained from 140 cases of triple negative breast cancer. A tissue microarray was constructed and immunohistochemistry for ER, PR, HER2, ALDH1, EZH2, CK5, CK14, EGFR, p63, caveolin, and p53 was performed. Tumour cell and stromal expression of ALDH1 were evaluated. Multivariate analysis was conducted, including all significant variables.Results: The majority of triple negative breast cancers were invasive ductal carcinomas of no special type (NST) (116/140). Tumour cells exhibited cytoplasmic expression of ALDH1 in 26 of 140 cases, while stromal expression was detected in 117 of 140 cases. Tumour cell expression did not correlate with any of the parameters. Conversely, stromal expression was associated with better overall survival (p=0.044). Assessment by Cox Regression Model showed a HR of 2.80 (HR = 1/0.357 = 2.80; 95%CI 0.178-0.714; p=0.004) for breast cancer death when ALDH1 was not found in the stromal compartment of tumours, independent of age, histological type/grade, nodal status, stage, relapse, and expression of basal markers. High EZH2 expression was noted in 120 of 140 triple negative breast cancers and was not associated with other variables. Basal-like cancers comprised 75% (105/140) of triple negative breast cancers. Interestingly, we found association between EZH2 and CK14 expression (p=0.041).Conclusions: ALDH1 expression is frequent in tumour-associated stromal cells of triple negative breast cancer and is associated with better outcome. Tumour microenvironment should be considered when studying prognostic impact of CSCs in breast cancer.