Clinicopathological and molecular pathological characteristics in tamoxifen‑related endometrial cancer

Saeki,Harumi; Horimoto,Yoshiya; Hlaing,May Thinzar; Men,Yuan; Rong,Lu; Ishizuka,Yumiko; Uomori,Toshitaka; Yoshida,Emiko; Terao,Yasuhisa; Arakawa,Atsushi; Saito,Tsuyoshi; Yao,Takashi

doi:10.3892/ol.2023.14142

Clinicopathological and molecular pathological characteristics in tamoxifen‑related endometrial cancer

Authors:
- Harumi Saeki
- Yoshiya Horimoto
- May Thinzar Hlaing
- Yuan Men
- Lu Rong
- Yumiko Ishizuka
- Toshitaka Uomori
- Emiko Yoshida
- Yasuhisa Terao
- Atsushi Arakawa
- Tsuyoshi Saito
- Takashi Yao
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Affiliations: Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113‑0033, Japan, Department of Breast Oncology, Juntendo University Faculty of Medicine, Tokyo 113‑0033, Japan, Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113‑0033, Japan, Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo 113‑0033, Japan
Published online on: November 9, 2023 https://doi.org/10.3892/ol.2023.14142
Article Number: 9
Copyright: © Saeki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tamoxifen (TAM), a selective estrogen receptor modulator, is often used for long‑term adjuvant endocrine therapy in patients with hormone receptor‑positive breast cancer. TAM is known to increase the risk of endometrial cancer (EC); however, the mechanism has not yet been fully elucidated. Therefore, molecular genetic analysis of EC following TAM administration (TAM‑related EC) was conducted. A total of 10 samples of TAM‑related EC and 20 sporadic EC samples (as controls) were analyzed. Copy number variation analysis was conducted, microsatellite instability (MSI) status was assessed, and mismatch repair (MMR) protein expression was examined immunohistochemically. Copy number variation analysis revealed that KDR, NOTCH1, NTRK1, NTRK3 and PDGFRB were more frequently amplified in TAM‑related EC (P=0.039, P<0.001, P=0.011, P=0.006 and P=0.035, respectively). In MSI analysis, 4 cases were classified as MSI‑high (40%), which is a higher frequency compared with that among patients with sporadic EC (~10% in Japanese women). Loss of MMR proteins was confirmed in all MSI‑high cases. In 1 MSI‑high case, a benign lesion of hyperplasia prior to EC development was also MSI‑high with loss of some MMR protein expression. Several genes were specifically amplified in TAM‑related ECs. Furthermore, TAM‑related ECs were frequently MSI‑high. Further studies are required to be conclusive; however, the present findings may lead to a reduction of unnecessary gynaecological testing in clinical practice and also encourage the testing for MSI status for optimal individualized treatment.

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