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

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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5 Citations (Scopus)


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 neoad‑ juvantchemotherapyandotherclinicalfactorsontheexpression 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 overexpres‑ sion was revealed to be common among patients with ovarian cancer, especially in those with non‑HGSC histology. In addi‑ tion, HER3 expression may be promoted by chemotherapy. These findings suggested that patients with ovarian cancer are good candidates for emerging HER3‑targeting therapies.

Original languageEnglish
Article number336
JournalOncology Letters
Issue number6
Publication statusPublished - Oct 7 2020
Externally publishedYes


  • Biomarker
  • HER3 protein expression
  • High‑grade serous carcinoma
  • Neoadjuvant chemotherapy
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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