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Overexpression of HER2/HER3 and clinical feature of ovarian cancer

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 corr...

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Autores principales: Chung, Ye Won, Kim, Seongmin, Hong, Jin Hwa, Lee, Jae Kwan, Lee, Nak Woo, Lee, Young Seok, Song, Jae Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658608/
https://www.ncbi.nlm.nih.gov/pubmed/31328457
http://dx.doi.org/10.3802/jgo.2019.30.e75
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author Chung, Ye Won
Kim, Seongmin
Hong, Jin Hwa
Lee, Jae Kwan
Lee, Nak Woo
Lee, Young Seok
Song, Jae Yun
author_facet Chung, Ye Won
Kim, Seongmin
Hong, Jin Hwa
Lee, Jae Kwan
Lee, Nak Woo
Lee, Young Seok
Song, Jae Yun
author_sort Chung, Ye Won
collection PubMed
description 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.
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spelling pubmed-66586082019-09-01 Overexpression of HER2/HER3 and clinical feature of ovarian cancer Chung, Ye Won Kim, Seongmin Hong, Jin Hwa Lee, Jae Kwan Lee, Nak Woo Lee, Young Seok Song, Jae Yun J Gynecol Oncol Original Article 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. Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology 2019-03-25 /pmc/articles/PMC6658608/ /pubmed/31328457 http://dx.doi.org/10.3802/jgo.2019.30.e75 Text en Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Chung, Ye Won
Kim, Seongmin
Hong, Jin Hwa
Lee, Jae Kwan
Lee, Nak Woo
Lee, Young Seok
Song, Jae Yun
Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title_full Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title_fullStr Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title_full_unstemmed Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title_short Overexpression of HER2/HER3 and clinical feature of ovarian cancer
title_sort overexpression of her2/her3 and clinical feature of ovarian cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658608/
https://www.ncbi.nlm.nih.gov/pubmed/31328457
http://dx.doi.org/10.3802/jgo.2019.30.e75
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