J Gynecol Oncol.  2019 Sep;30(5):e75. 10.3802/jgo.2019.30.e75.

Overexpression of HER2/HER3 and clinical feature of ovarian cancer

• Chung YW
• Kim S
• Hong JH
• Lee JK
• Lee NW
• Lee YS
• Song JY

• KMID: 2457153
• DOI: http://doi.org/10.3802/jgo.2019.30.e75

Abstract

OBJECTIVES
Human epidermal growth factor receptor-2 (HER2) and 3 (HER3) belong to the epidermal growth factor receptor (EGFR) family of transmembrane receptor tyrosine kinases. In this study, we assessed HER2/HER3 expression levels in specimens of epithelial ovarian cancer and determined their correlation with clinical features of ovarian cancer.
METHODS
Tissue microarrays (TMAs) were prepared from paraffin blocks of 105 ovarian tumour samples. HER2, HER3, PI3K, Akt, p-Akt, mTOR, p-mTOR, S6, and p-S6 expression levels were investigated using immunohistochemistry (IHC). HER2 and HER3 amplifications were determined using in situ hybridization (ISH). The correlation between HER2/3 expression and disease outcome of the patients including surgical outcome, progression-free survival (PFS) and overall survival (OS) was analysed.
RESULTS
HER2 positivity was 3.8% by IHC and 5.7% by ISH, whereas that of HER3 was 12.4% and 8.6%, respectively. HER2 status by either IHC or ISH was not related to PFS (p=0.128, 0.168, respectively) and OS (p=0.245, 0.164, respectively). However, the HER3 status determined using fluorescence ISH was associated with poor PFS (p=0.035 on log rank test), which was a significant risk factor even after adjusting other possible risk factors in multivariate analysis (hazard ratio=2.377 [1.18-7.49], p=0.021). Expressions of Akt, p-mTOR, and S6 were also related with poor progression (p=0.008, 0.049, 0.014, respectively).
CONCLUSION
HER3 is possibly an independent marker for poor prognosis in individuals with ovarian cancer, as the HER3 signalling pathway is distinct from that of HER2. The possibility of targeted therapy for patients with HER3 alteration in ovarian cancer should be evaluated.

Keyword

Ovarian Cancer; Immunohistochemistry; In Situ Hybridization

MeSH Terms

Disease-Free Survival
Epidermal Growth Factor
Fluorescence
Humans
Immunohistochemistry
In Situ Hybridization
Multivariate Analysis
Ovarian Neoplasms*
Paraffin
Phosphotransferases
Prognosis
Receptor, Epidermal Growth Factor
Risk Factors
Tyrosine
Epidermal Growth Factor
Paraffin
Phosphotransferases
Receptor, Epidermal Growth Factor
Tyrosine