Ovarian cancer is the deadliest gynecological
malignancy in Western countries. Early detection, however, is hampered by the fact that the origin of
ovarian cancer remains unclear. Knowing that in a high percentage of endometrioid
ovarian cancers Wnt/β-
catenin signaling is activated, and in view of the hypothesis that
ovarian cancer may originate from the distal oviduct, we studied mice in which Wnt/β-
catenin signaling was activated in Müllerian duct-derived tissues. Conditional
adenomatous polyposis coli (Apc) knockout mice were used to study the activation of Wnt/β-
catenin signaling in Müllerian duct-derived organs. These Pgr(Cre/+);Apc(ex15lox/lox) mice (n = 44) were sacrificed
at 10, 20, 40 and 80 weeks and uterus, oviduct, ovaries and surrounding fat tissues were assessed using immunohistochemistry. Using nuclear β-
catenin staining, Wnt/β-
catenin signaling activation was confirmed in the entire epithelium of the adult Müllerian duct (fimbriae, oviduct and endometrium), but was absent in ovarian surface epithelium cells (OSEs). Besides
endometrial hyperplasia, in 87.2% of mice intraepithelial lesions of the distal oviduct were found, whereas OSEs remained unaffected. In addition, 62.5% of mice developed
tumors in the distal and fimbrial part of the oviduct. In the ovaries, mainly at young age, in 16.3% of mice, simple epithelial
cysts were noted, which developed further into endometrioid ovarian
tumors, resembling human endometrioid
ovarian cancer (27.9% of mice). Next to this, locoregional growth in the utero-ovarian ligament was also shown. Here, for the first time, mutations (activation of Wnt/β-
catenin) in the distal oviduct result in precursor lesions that develop into ovarian
tumors, resembling human endometrioid
ovarian cancer.