Overexpression of HER2/HER3 and clinical feature of ovarian cancer

Ye Won Chung, Seongmin Kim, Jin Hwa Hong, Jae Kwan Lee, Nak Woo Lee, Young Seok Lee, Jae Yun Song

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    45 Citations (Scopus)

    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.

    Original languageEnglish
    Article numbere75
    JournalJournal of gynecologic oncology
    Volume30
    Issue number5
    DOIs
    Publication statusPublished - 2019 Sept

    Bibliographical note

    Funding Information:
    This study was funded by the Korea Ministry of Environment (MOE) as ‘The Environmental Health Action Program’ (2016001360007).

    Publisher Copyright:
    © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

    Keywords

    • Immunohistochemistry
    • In Situ Hybridization
    • Ovarian Cancer

    ASJC Scopus subject areas

    • Oncology
    • Obstetrics and Gynaecology

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