Genetic features of endometrioid-type endometrial carcinoma arising in uterine adenomyosis

This study aimed to clarify the genetic features of endometrioid-type endometrial cancer arising in adenomyosis (EC-AIA) using targeted sequencing and immunohistochemistry (IHC) for both carcinoma and adjacent adenomyosis tissues. We identified three endometrioid-type EC-AIAs in 689 patients with endometrial cancer; two exhibited grade 3 endometrioid carcinoma. IHC revealed retained expression of PMS2, MSH6, ARID1A, and PAX2. Two of them showed diffuse strong p53 expression only in the carcinoma. PTEN expression was lost in carcinoma of only one of these cases. Carcinoma had many gene mutations than adjacent adenomyosis in all cases. KRAS and TP53 mutations were found in two of them. The other patient had mutations in KRAS, PIK3CA, and PPP2R1A. They were classified as two “p53-mutated” and one “non-specific molecular profile.” These molecular alterations in endometrioid-type EC-AIA imply similar carcinogenesis to a subset of endometrial endometrioid carcinoma and might be used as targets of liquid biopsy after further validation. Availability of data and material The data that support the findings of this study are available from the corresponding author upon reasonable request. Code availability Not applicable.

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The authors are grateful to Hitoshi Ichikawa, Sachiyo Mitani, Maiko Masuda, Yoko Shimada, and to other physicians and staff at the National Cancer Center and other hospitals for their help and support. We also thank Editage for English language editing of this manuscript. Funding KAKENHI-19K16572, National Cancer Center Research and Development Fund (29-A-2, NCC Biobank, and NCC Core Facility). Author information Authors and Affiliations Contributions Hiroshi Yoshida: conceptualization, methodology, formal analysis, investigation, resources, data curation, writing–original draft, writing–review and editing. Yuka Asami: formal analysis, resources, data curation, writing–review, and editing. Mayumi Kobayashi-Kato: resources, data curation, writing–review, and editing. Yasuhito Tanase: resources, data curation, writing–review, and editing. Masaya Uno: resources, data curation, writing–review, and editing. Mitsuya Ishikawa: resources, data curation, writing–review, and editing. Kouya Shiraishi: conceptualization, methodology, formal analysis, investigation, resources, data curation, writing–original draft, writing–review and editing. Tomoyasu Kato: resources, data curation, writing–review, and editing. Corresponding author Ethics declarations Ethics approval This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and was approved (2017–136) by the institutional review board of the National Cancer Center, Tokyo, Japan. Consent to participate The need for written informed consent was waived owing to the retrospective nature of the study. Consent for publication The need for written informed consent was waived owing to the retrospective nature of the study. Conflict of interest The authors declare no competing interests. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. 428_2021_3234_MOESM1_ESM.tif (download TIF ) Supplementary Fig. 1 Pathological findings of Cases 2 and 3. In case 2, a dilated cyst contains tumor cell is observed in the deep cervical stroma (a). Endometrioid carcinoma exhibits glandular and papillary structure in the cyst of adenomyosis (b). Case 3: Endometrioid carcinoma shows fused glands and solid nests (c). Tumor cells do not show diffuse strong p16 positivity (d). Supplementary file1 (TIF 5542 KB) Rights and permissions About this article Cite this article Yoshida, H., Asami, Y., Kobayashi-Kato, M. et al. Genetic features of endometrioid-type endometrial carcinoma arising in uterine adenomyosis. Virchows Arch 481, 117–123 (2022). https://doi.org/10.1007/s00428-021-03234-y Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00428-021-03234-y