Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer

Mizuno,Takaaki; Kojima,Yuki; Yonemori,Kan; Yoshida,Hiroshi; Sugiura,Yukiko; Ohtake,Yohei; Okuma,Hitomi S.; Nishikawa,Tadaaki; Tanioka,Maki; Sudo,Kazuki; Shimomura,Akihiko; Noguchi,Emi; Kato,Tomoyasu; Shimoi,Tatsunori; Uno,Masaya; Ishikawa,Mitsuya; Fujiwara,Yasuhiro; Ohe,Yuichiro; Tamura,Kenji

doi:10.3892/ol.2020.12200

Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer

Authors:
- Takaaki Mizuno
- Yuki Kojima
- Kan Yonemori
- Hiroshi Yoshida
- Yukiko Sugiura
- Yohei Ohtake
- Hitomi S. Okuma
- Tadaaki Nishikawa
- Maki Tanioka
- Kazuki Sudo
- Akihiko Shimomura
- Emi Noguchi
- Tomoyasu Kato
- Tatsunori Shimoi
- Masaya Uno
- Mitsuya Ishikawa
- Yasuhiro Fujiwara
- Yuichiro Ohe
- Kenji Tamura
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Affiliations: Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo 104‑0045, Japan, Department of Pathology, National Cancer Center Hospital, Tokyo 104‑0045, Japan, Department of Gynecology, National Cancer Center Hospital, Tokyo 104‑0045, Japan, The Jikei University Graduate School of Medicine, Tokyo 105‑8461, Japan
Published online on: October 7, 2020 https://doi.org/10.3892/ol.2020.12200
Article Number: 336
Copyright: © Mizuno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

HER3 (erbB3) signaling serves an important role in the development and chemoresistance of ovarian cancer, and is activated by chemotherapy. To evaluate the influence of neoadjuvant chemotherapy and other clinical factors on the expression of HER3, as well as to examine its role as a prognostic marker, the present study evaluated archived tissues from patients who underwent surgery for ovarian cancer between 2011 and 2018 at our hospital. Immunohistochemical staining for HER3 was performed using formalin‑fixed paraffin‑embedded surgical specimens and biopsy samples. In total, data from 111 patients with sufficient surgically resected tumor samples were extracted. A total of 28 patients with histology type high‑grade serous carcinoma (HGSC) had specimens available from both pre‑chemotherapy biopsies and post‑chemotherapy surgery. High HER3 expression (HER3‑high) was observed in 64 patients (58%), whereas low HER3 expression (HER3‑low) was observed in 47 patients (42%). Multivariate logistic regression analysis identified neoadjuvant chemotherapy [odds ratio (OR), 7.49; 95% confidence interval (CI), 2.48‑22.64; P<0.001) and non‑HGSC histology (OR, 5.42; 95% CI, 1.99‑14.78; P<0.001) as significant predictive factors for HER3‑high. In pre‑chemotherapy biopsy specimens, 15 patients were HER3‑high and 13 were HER3‑low. After chemotherapy, eight of 13 patients with HER3‑low exhibited a change in status to HER3‑high, with a trend toward poorer progression‑free survival compared to that of patients whose status remained HER3‑low. In conclusion, HER3 overexpression was revealed to be common among patients with ovarian cancer, especially in those with non‑HGSC histology. In addition, HER3 expression may be promoted by chemotherapy. These findings suggested that patients with ovarian cancer are good candidates for emerging HER3‑targeting therapies.

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