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

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.