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74 Clinical impact of HER3/ERBB3 expression in primary and recurrent ovarian cancer
  1. Kota Yokosu1,2,
  2. Kenichi Harano2,
  3. Riu Yamashita2,
  4. Satoshi Fujii3,
  5. Hiroshi Tanabe1,2,
  6. Toru Mukohara2,
  7. Saori Sato4,
  8. Maki Kobayashi5,
  9. Keiko Oshima5,
  10. Hiroko Kimura1,
  11. Hiroyuki Takahashi1,
  12. Motoaki Saito1,
  13. Kyosuke Yamada1,
  14. Hirokuni Takano1 and
  15. Aikou Okamoto1
  1. 1The Jikei University School of Medicine, Tokyo, Japan
  2. 2National Cancer Center Hospital East, Kashiwa, Japan
  3. 3Yokohama City University Graduate School of Medicine, Yokohama, Japan
  4. 4Daiichi Sankyo Co., Ltd., Tokyo, Japan
  5. 5Daiichi Sankyo RD Novare Co., Ltd., Tokyo, Japan


Introduction/Background HER3/ERBB3 is implicated in chemoresistance in ovarian cancer. While most previous studies have examined primary tumors only, this retrospective study examined HER3 expression using samples from both primary and recurrent tumors to determine changes in HER3 expression through recurrence and its impact on prognosis.

Methodology Patients with available surgical specimens for both initial treatment (surgery and chemotherapy) and recurrent tumor resection for epithelial ovarian cancer between October 2000 and October 2018 were examined. HER3 protein expression status by immunohistochemical (IHC) staining (HER3) and HER3 mRNA expression status by nCounter (ERBB3) were investigated using matched-pair samples. IHC scores of 0 or 1+ were defined as HER3-low, and 2+ or 3+ as HER3-high. Patients were also divided into two groups based on median ERBB3 expression, defined as ERBB3-low and ERBB3-high. The prognostic values of HER3 and ERBB3 were evaluated based on recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and log-rank test.

Results In total, 56 patients were enrolled. There were 16/12/22/6 patients with FIGO stage I/II/III/IV, respectively. Nineteen patients had high-grade serous carcinoma, 14 had clear cell carcinoma (CCC), 11 had low-grade serous carcinoma, 8 had endometrioid carcinoma, and 4 had mucinous carcinoma. The overall rate of HER3-high was 62.5% at initial treatment and 72.2% at recurrence. CCC had the highest rates of HER3-high at 71.4% and 92.9%, respectively. HER3 at initial treatment did not statistically correlate with prognosis. HER3-high group at recurrence showed better OS (p=0.014). ERBB3-high group at initial treatment showed significantly better prognosis compared to ERBB3-low group in both RFS (p<0.01) and OS (p=0.018). ERBB3 at recurrence was significantly downregulated compared to initial treatment, and ERBB3 at recurrence did not statistically correlate with prognosis.

Conclusion Although ERBB3 at initial treatment was a favorable prognostic factor, its expression was downregulated at recurrence and no longer correlated with prognosis.

Disclosures This study was funded by Daiichi Sankyo Co., Ltd., and received technical support by Daiichi Sankyo RD Novare Co., Ltd.

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