Distinct β-Catenin and PIK3CA Mutation Profiles in Endometriosis-Associated Ovarian Endometrioid and Clear Cell Carcinomas

Toshihide Matsumoto, Masaaki Yamazaki, Hiroyuki Takahashi, Sabine Kajita, Erina Suzuki, Tomoko Tsuruta, Makoto Saegusa
American journal of clinical pathology · 2015 · vol. 144(3) , pp. 452–463 · doi:10.1309/ajcpz5t2poofmqvn · PMID:26276776 · W2340936662
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Endometrioid ovarian carcinomas and their associated endometriosis showed distinct β-catenin mutations absent in clear cell types, while both tumor types harbored different PIK3CA mutations found in coexisting endometriosis.

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Abstract

OBJECTIVES: We focused on the differences in molecular mechanisms in the early stages of endometriosis-associated ovarian endometrioid carcinoma (OEMCa) and ovarian clear cell carcinoma (OCCCa). METHODS: Alterations in the β-catenin and PIK3CA genes, as well as expression of their associated markers, were investigated. RESULTS: Mutations in exon 3 of the β-catenin gene were identified in 21 (60%) of 35 OEMCas. The mutations were also detected in the coexisting nonatypical (52.4%) and atypical (73.3%) endometriosis, and the single-nucleotide substitutions were identical in most cases. In contrast, the mutations were not identified in any of the OCCCas and their coexisting endometriosis. PIK3CA mutations were observed in 11 (31.4%) of 35 OEMCas and 10 (35.7%) of 28 OCCCas. Ten of 11 OEMCas had PIK3CA mutations in exon 9, and eight of 10 OCCCas had them in exon 20. The same mutations were also detected in the coexisting nonatypical and/or atypical endometriosis in three OEMCas and four OCCCas. In addition, significant differences in the expression of pAkt, hepatocyte nuclear factor 1β, hypoxia-inducible factor 1α, p65, and inducible nitric oxide synthase were evident between the two types of tumors and their coexisting endometriosis. CONCLUSIONS: Distinct molecular events may occur in relatively early stages of tumorigenesis of endometriosis-associated OEMCas and OCCCas.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Adenocarcinoma, Clear Cell beta Catenin Carcinoma, Endometrioid Endometriosis Mutation Neoplasms, Glandular and Epithelial Ovarian Neoplasms Phosphatidylinositol 3-Kinases Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adult Aged beta Catenin Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Ovarian Epithelial Cell Transformation, Neoplastic

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