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HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value

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Abstract

The clinical and prognostic significance of HER3 expression and its relation to HER2 status in primary colorectal cancer (pCRC) were investigated. We retrospectively analysed 365 consecutive cases of pCRC that had been previously evaluated for HER2 status and included their 143 matched lymph node metastases. Immunohistochemistry (IHC) was performed to assess HER3 expression using tissue array methods. Of 364 eligible patients, HER3 overexpression was detected in 251 cases (69 %) (IHC 2+, n = 186 and IHC 3+, n = 65). HER3 overexpression was inversely correlated with histologic grade (p = 0.006), tumour size (p < 0.001), tumour depth (p < 0.001), TNM stage (p = 0.002), lymphatic invasion (p = 0.004), lymph node metastasis (p = 0.013) and distant metastasis (p = 0.039). Moreover, it positively correlated with both HER2 overexpression (p = 0.007) and HER2 gene amplification (p = 0.006). Although HER3 overexpression was associated with longer survival in univariate analysis (p = 0.026), it was not an independent prognostic factor in multivariate analysis (p = 0.359). Moreover, co-alteration of HER3 and HER2 was associated with neither survival nor any clinicopathologic parameter except tumour location in the rectum. Although not an independent prognostic factor for overall survival, HER3 overexpression was associated with several favourable prognostic clinicopathologic parameters. Additionally, HER3 overexpression strongly correlated with HER2 positivity in this cohort of patients.

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Acknowledgments

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI14C1813).

Conflict of interest

The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea

    An Na Seo

  2. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Yoonjin Kwak, Woo Ho Kim & Gheeyoung Choe

  3. Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea

    Duck-Woo Kim & Sung-Bum Kang

  4. Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea

    Hye Seung Lee

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  1. An Na Seo
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Correspondence to Hye Seung Lee.

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Supplementary Table S1

Demographic characteristics of patients (DOCX 18 kb)

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Seo, A.N., Kwak, Y., Kim, W.H. et al. HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value. Virchows Arch 466, 645–654 (2015). https://doi.org/10.1007/s00428-015-1747-2

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