Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma
Autor: | Kazuto Nishio, Kazuko Sakai, Yasushi Kotani, Noriomi Matsumura, Hisamitsu Takaya, Hidekatsu Nakai, Chiho Miyagawa, Akiko Kanto, Kosuke Murakami |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Adult Pathology medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases DNA Mutational Analysis Endometriosis medicine.disease_cause Polymerase Chain Reaction Article Pathology and Forensic Medicine 03 medical and health sciences Endometrium 0302 clinical medicine Ovarian cancer Ovarian carcinoma medicine Biomarkers Tumor Humans neoplasms Microdissection Early Detection of Cancer Ovarian Neoplasms Mutation business.industry Cancer Oncogenes Middle Aged medicine.disease Serous fluid 030104 developmental biology 030220 oncology & carcinogenesis Clear cell carcinoma Female business Adenocarcinoma Clear Cell |
Zdroj: | Modern Pathology |
ISSN: | 1530-0285 0893-3952 |
Popis: | 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. |
Databáze: | OpenAIRE |
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