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Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy

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Abstract

Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealed HER2 gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Japan Agency for Medical Research and Development (AMED), “Clinical research and clinical trial promotion research project Cancer research and development expenses (28-A-12).” The STATICE trial was funded by the Japan Agency for Medical Research and Development (AMED), and Daiichi Sankyo Co., Ltd. DS-8201a was provided by Daiichi Sankyo Co., Ltd.

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Author notes

  1. Hiroshi Yoshida and Tadaaki Nishikawa contributed equally to this work.

Authors and Affiliations

  1. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hiroshi Yoshida

  2. Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Tadaaki Nishikawa & Kan Yonemori

  3. Medical Oncology Division, Ambulatory Chemotherapy Center, Hyogo Cancer Center, Kitaoji-cho, Akashi, Hyogo, Japan

    Koji Matsumoto

  4. Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Aichi, Japan

    Masahiko Mori

  5. Division of Gynecology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan

    Yasuyuki Hirashima

  6. Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Minamiumemoto-machi, Matsuyama, Ehime, Japan

    Kazuhiro Takehara

  7. Gynecology Service, National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka, Japan

    Kazuya Ariyoshi

  8. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Yamane, Hidaka, Saitama, Japan

    Kosei Hasegawa

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  1. Hiroshi Yoshida
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  2. Tadaaki Nishikawa
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  3. Koji Matsumoto
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  9. Kan Yonemori
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Contributions

Hiroshi Yoshida: conceptualization, methodology, formal analysis, investigation, resources, data curation, writing (original draft), and writing (review and editing). Tadaaki Nishikawa: formal analysis, resources, data curation, and writing (review and editing). Koji Matsumoto: resources, data curation, and writing (review and editing). Masahiko Mori: resources, data curation, and writing (review and editing). Yasuyuki Hirashima: resources, data curation, and writing (review and editing. Kazuhiro Takehara: resources, data curation, and writing (review and editing). Kazuya Ariyoshi: resources, data curation, and writing (review and editing). Kosei Hasegawa: resources, data curation, and writing (review and editing. Kan Yonemori: resources, data curation, and writing (review and editing)

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Correspondence to Hiroshi Yoshida.

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All study participants provided informed consent, and the present study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and with approved protocols (2014-393) by the institutional Review Board of the National Cancer Center, Tokyo, Japan.

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Evaluation of histopathological details of HER2 expression in uterine carcinosarcoma (PNG 2839 kb)

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Yoshida, H., Nishikawa, T., Matsumoto, K. et al. Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy. Virchows Arch 478, 1161–1171 (2021). https://doi.org/10.1007/s00428-021-03017-5

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