ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021
Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 19 citations in OpenAlex.
- Spatial heterogeneity of hotspot mutations and clonal relatedness in ovarian endometrioid carcinoma.Molecular oncology · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Review
- Molecular profile and targeted therapies for ovarian clear cell ovarian cancer.Therapeutic advances in medical oncology · 2026Review
- Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution.Communications biology · 2025Article
- Overexpression of FOS enhances the malignant potential of eutopic endometrial stromal cells in patients with endometriosis‑associated ovarian cancer.Oncology reports · 2025Article
- Review
- The expression of autophagy-related gene CXCL12 in endometriosis associated ovarian cancer and pan-cancer analysis.Frontiers in endocrinology · 2025Article
- Review
- The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.Frontiers in immunology · 2024Review
- The role of peroxisome proliferator-activated receptors in endometriosis.Frontiers in medicine · 2024Review
- Frequent PIK3CA mutation in normal endometrial gland drives spheroid formation and may be involved in stem cell propagation.Cancer science · 2023Article
- Review the progression of ovarian clear cell carcinoma from the perspective of genomics and epigenomics.Frontiers in genetics · 2023Review
- New Understanding of Diagnosis, Treatment and Prevention of Endometriosis.International journal of environmental research and public health · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Recent studies have reported cancer-associated mutations in normal endometrium. Mutations in eutopic endometrium may lead to endometriosis and endometriosis-associated ovarian cancer. We investigated PIK3CA mutations (PIK3CAm) for three hotspots (E542K, E545K, H1047R) in eutopic endometrium in patients with ovarian cancer and endometriosis from formalin-fixed paraffin-embedded specimens by laser-capture microdissection and droplet digital PCR. The presence of PIK3CAm in eutopic endometrial glands with mutant allele frequency ≥ 15% were as follows: ovarian clear cell carcinoma (OCCC) with PIK3CAm in tumors, 20/300 hotspots in 11/14 cases; OCCC without PIK3CAm, 42/78 hotspots in 11/12 cases; high-grade serous ovarian carcinoma, 8/45 hotspots in 3/5 cases; and endometriotic cysts, 5/63 hotspots in 5/6 cases. These rates were more frequent than in noncancer nonendometriosis controls (7/309 hotspots in 5/17 cases). In OCCC without PIK3CAm, 7/12 (58%) cases showed multiple hotspot mutations in the same eutopic endometrial glands. In 3/54 (5.6%) cases, PIK3CAm was found in eutopic endometrial stroma. Multisampling of the OCCC tumors with PIK3CAm showed intratumor heterogeneity in three of eight cases. In two cases, PIK3CAm was detected in the stromal component of the tumor. Homogenous PIK3CAm in the epithelial component of the tumor matched the mutation in eutopic endometrial glands in only one case. Eutopic endometrial glands in ovarian cancer and endometriosis show high frequency of PIK3CAm that is not consistent with tumors, and multiple hotspot mutations are often found in the same glands. While the mutations identified in eutopic endometrium may not be driver mutations in the patient's cancer, these are still driver mutations but this specific clone has not undergone the requisite steps for the development of cancer.
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