ALDH1A1 Expression in the Pathogenesis of Ovarian Carcinoma

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Discussion

ALDH1A1 has been proposed as a marker for cancer stem cells or cancer initiating cells in various types of human cancer, including ovarian carcinoma. Previous experimental work demonstrated ALDH1A1-positive ovarian cancer cells to be more tumorigenic than ALDH1A1-negative cells.^[22,23] It is therefore plausible that these ALDH1A1-expressing tumor cells may be derived from somatic stem cells, likely from the fallopian tube. Indeed, the mouse ovarian hilum has recently been shown to be enriched for ALDH1A1-positive stem cells with increased susceptibility to malignant transformation.^[16] The purpose of this study was to comprehensively characterize the expression of ALDH1A1 in normal human fallopian tube, tubal–mesothelial junctions, ovarian surface epithelium, and in lesions thought to represent different stages of tumor progression - namely, p53 signatures, serous tubal intraepithelial carcinoma, and primary and recurrent high-grade serous carcinomas.......

...... In summary, we demonstrate that ALDH1A1-expressing epithelial cells are abundant in the normal fallopian tube, but not in p53 signatures or serous tubal intraepithelial carcinoma. ALDH1A1-positive cells can occasionally be observed in some high-grade serous carcinomas, but usually restricted to only a few tumor cells. These findings suggest that ALDH1A1 is probably not a specific marker for fallopian tube stem cells, and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma. Identification of more specific markers of Müllerian epithelial stem cells is necessary to identify the putative somatic stem cell population involved in the pathogenesis of this malignancy