首页 > 期刊杂志 > 正文

Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma.

ALDH1A1表达丢失是卵巢高级别浆液性癌发病机制中的一个早期事件

Chui MH,Wang Y,Wu RC,Seidman J,Kurman RJ,Wang TL,Shih IeM

Abstract

Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this study, we used immunohistochemistry to assess the distribution of ALDH1A1 staining in the epithelium of human fallopian tubes, with particular reference to the transition of tubal epithelium to mesothelium (ie, tubal-mesothelial junction), ovarian surface epithelium, as well as putative precursors of ovarian high-grade serous carcinoma, namely, serous tubal intraepithelial carcinoma and 'p53 signatures,' and overt serous carcinoma. Expression of ALDH1A1 was detected in both secretory and ciliated tubal epithelial cells, tubal-mesothelial junctions and ovarian surface epithelium, but was absent in serous tubal intraepithelial carcinoma and p53 signatures. Positive staining in high-grade serous carcinoma, when present, was typically limited to rare tumor cells. In silico analyses of the mRNA expression data set from The Cancer Genome Atlas revealed downregulation of ALDH1A1 transcripts in high-grade serous carcinoma relative to normal tubal epithelium, and no association between ALDH1A1 expression levels and overall survival. Our results do not support ALDH1A1 as a specific marker of stem cells in human fallopian tube and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma.

摘要

肿瘤起始细胞被认为与正常体细胞中性干细胞存在一些共同之处。小鼠卵巢门的干细胞已被证实表达一种干细胞的标志物——乙醛脱氢酶1A1亚型,并且具有恶性转化倾向。这项发现与人类的潜在关联性还未得到证实。在这个研究中,我们使用免疫组化技术检测输卵管上皮中ALDH1A1的染色分布,特别是在输卵管上皮与间皮交界地带(如输卵管间皮连接处)、卵巢表面上皮、卵巢高级别浆液性癌假定前体——存在p53基因异常的浆液性输卵管上皮内癌和典型的浆液性癌处。ALDH1A1能在分泌性和有纤毛的输卵管上皮细胞、输卵管间皮连接处和卵巢表面上皮中检测到,但在p53基因异常的浆液性输卵管上皮内癌中缺失。在高级别浆液性癌中的阳性染色通常局限在少数肿瘤细胞中。来自The Cancer Genome Atlas的mRNA芯片检测提示与正常输卵管上皮相比,高级别浆液性癌中ALDH1A1的转录水平是下调的,而且ALDH1A1表达水平与总生存率无关。我们的结论不支持ALDH1A1作为输卵管上皮干细胞的特殊标志物,而是证明了其表达丢失是高级别浆液性癌进展中的一个早期事件。

full text

我要评论

0条评论