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干细胞标志物醛脱氢酶1(ALDH1)的高表达与浸润性乳腺癌中BRCA1的减少有关。

High expression of stem cell marker ALDH1 is associated with reduced BRCA1 in invasive breast carcinomas.

作者信息

Madjd Zahra, Ramezani Babak, Molanae Saadat, Asadi-Lari Mohsen

机构信息

Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Asian Pac J Cancer Prev. 2012;13(6):2973-8. doi: 10.7314/apjcp.2012.13.6.2973.

Abstract

BACKGROUND

Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1.

METHODS

We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status.

RESULTS

Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics.

CONCLUSION

Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

摘要

背景

癌症干细胞(CSC)已在包括乳腺癌在内的多种恶性肿瘤中被描述。在多种标志物中,醛脱氢酶1(ALDH1)已被确定为乳腺癌干细胞的可靠标志物。原发性乳腺上皮细胞中BRCA1的敲低导致表达ALDH1的细胞增加。

方法

我们使用免疫组织化学检查了127例乳腺癌中ALDH1的表达,并将其与临床病理参数以及BRAC1状态相关联。

结果

比较ALDH1和BRCA1表达的结果显示两者之间存在显著的负相关,表明在表达ALDH1的乳腺癌细胞中更常出现BRCA1降低的情况(p值 = 0.044)。共有24/110(22%)的肿瘤表现出ALDH1 + / BRCA1 -/低表型,这显示出与高级别存在关联的趋势(p值 = 0.056)。ALDH1的细胞质表达与肿瘤特征无关。

结论

综上所述,我们的研究结果表明,在一系列未经选择的乳腺癌中,ALDH1增加与BRCA1降低呈负相关。因此,具有BRCA1表型降低的ALDH1阳性(癌症干细胞)细胞可能表明一部分患者,针对这些患者,对癌症干细胞标志物ALDH1进行特异性靶向治疗以及更积极的辅助治疗是合适的。

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