HER3 protein expression as a risk factor for post-operative recurrence in patients with early-stage adenocarcinoma and adenosquamous carcinoma of the cervix

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

doi:10.3892/ol.2020.11899

HER3 protein expression as a risk factor for post-operative recurrence in patients with early-stage adenocarcinoma and adenosquamous carcinoma of the cervix

Oncol Lett. 2020 Oct;20(4):38. doi: 10.3892/ol.2020.11899. Epub 2020 Jul 23.

Authors

Takaaki Mizuno^{1

2}, Yuki Kojima¹, Kan Yonemori¹, Hiroshi Yoshida³, Yukiko Sugiura⁴, Yohei Ohtake¹, Hitomi S Okuma¹, Tadaaki Nishikawa¹, Maki Tanioka¹, Kazuki Sudo¹, Akihiko Shimomura¹, Emi Noguchi¹, Tomoyasu Kato⁴, Tatsunori Shimoi¹, Masaya Uno⁴, Mitsuya Ishikawa⁴, Yasuhiro Fujiwara¹, Yuichiro Ohe², Kenji Tamura¹

Affiliations

¹ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
² Cancer Medicine, Jikei University Graduate School of Medicine, Tokyo 105-8461, Japan.
³ Department of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
⁴ Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan.

Abstract

Patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC) have a poorer prognosis than those with squamous cell carcinoma (SCC). Erb-b2 receptor tyrosine kinase 3 (HER3) is a member of the epidermal growth factor receptor family and its expression is associated with unfavorable prognosis in several cancer types, including SCC of the cervix. As there is limited information on the prognostic value of HER3 for AC and ASC of the cervix, the present study aimed to evaluate the expression of HER3 and its impact on post-operative recurrence in patients with AC and ASC of the cervix. This retrospective study included 39 patients with early-stage AC and ASC who underwent primary surgery between January 1997 and December 2017. Immunohistochemical staining for HER3 was performed on formalin-fixed paraffin-embedded surgical specimens. The possible influence of HER3 expression on disease-free survival (DFS) was studied by using multivariate Cox regression with adjustment for established risk factors of post-operative recurrence. High expression of HER3 (HER3-high) was detected in 85.1% of cases of AC (23/27) and in 58.3% of cases of ASC (7/12). The median follow-up duration was 63.1 months and Kaplan-Meier analysis indicated that the 5-year DFS rates of patients with AC and ASC of the cervix were 56.7% in patients with HER3-high and 77.8% in patients with HER3-low (log rank, P=0.20). On multivariate analysis, HER3-high [hazard ratio (HR)=6.32, 95% CI: 1.10-36.26, P=0.039), pelvic lymph node metastasis (HR=7.61, 95% CI: 2.07-28.00, P=0.002) and vascular invasion (HR=4.28, 95% CI: 1.12-16.31, P=0.033) were indicated to be independent predictors of DFS. To date, the present study is the most comprehensive analysis to evaluate the expression of HER3 in patients with early-stage AC and ASC of the cervix. The results suggested that HER3 overexpression may be an independent risk factor for post-operative recurrence. However, these results and the prognostic value of HER3 should be confirmed in a larger sample.

Keywords: HER3 protein expression; biomarker; cervical cancer; prognostic factor.