Alterations in β-catenin, microsatellite instability, and HNF-1β levels are independently associated with ovarian endometriosis–associated tumorigenesis

Tomohiro M, Mikihisa Tomohiro, Toshihide Matsumoto, Matsumoto T, Rinako Miura, Miura R, Oguri Y, Yasuko Oguri, Yokoi A, Ako Yokoi, Masataka Tochimoto, Tochimoto M, Saegusa M, Makoto Saegusa
Human pathology · 2019 · vol. 89 , pp. 10–23 · doi:10.1016/j.humpath.2019.04.001 · PMID:31022415 · W2942227780
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This study investigated the molecular alterations in β-catenin, microsatellite instability, and HNF-1β and found them to be independently linked to the development of ovarian endometriosis-associated tumors.

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Abstract

We focused on specific molecular events during the development of endometriosis-associated ovarian endometrioid carcinoma (OEmCa) and ovarian clear cell carcinoma (OCCCa). Alterations in β-catenin (encoded by CTNNB1) and microsatellite instability (MSI), as well as changes in the expression levels of HNF-1β and DNA mismatch repair (MMR) proteins were investigated in 50 OEmCas and 21 OCCCas with endometriotic lesions. Mutations of CTNNB1 were identified in 28 (56%) of the 50 OEmCa cases and 26 (41.9%) of the 62 coexisting endometriosis lesions. MSI-high (H) was observed in 7 (14.6%) of the 48 OEmCa and 14 (23.3%) of the 60 coexisting endometriosis, and was significantly associated with loss of MMR protein expression, but not CTNNB1 mutations. Nonidentical CTNNB1 status between 2 different epithelial lesions within endometriosis was observed in 8 of 10 informative endometriosis cases that had adjacent OEmCa. Similar findings for MSI features were also found in 2 of 3 informative cases, suggesting that endometriotic lesions may predominantly consist of polyclonal cells. In contrast, high HNF-1β expression was significantly associated with SLC3A1 expression, which plays a major role in HNF-1β-triggered induction of reactive oxygen species in OCCCas, independent of abnormalities in both β-catenin and MSI/MMR status. Finally, 4 inflammatory parameters associated with repeated hemorrhaging in endometriosis were significantly higher in endometriosis with MSI-high when compared with that with MSS, independent of both β-catenin and HNF-1β status. In conclusion, different molecular pathways including alterations in β-catenin, MSI, and HNF-1β levels may contribute to tumorigenesis in endometriosis-associated carcinoma.

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Condition tags

endometriosis

MeSH descriptors

Carcinogenesis Endometriosis Ovarian Neoplasms Ovarian Neoplasms Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adult Aged beta Catenin beta Catenin beta Catenin Carcinogenesis Carcinogenesis Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Endometriosis

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