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Identification of the Coexisting HER2 Gene Amplification and Novel Mutations in the HER2 Protein-Overexpressed Mucinous Epithelial Ovarian Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC).

Methods

Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18–24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing.

Results

The FISH–IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases.

Conclusions

HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.

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Acknowledgment

This work was supported in parts by grants from Department of Health (DOH99-FDA-43002-H), Chung Shan Medical University (G098N0013) and Chung Shan Medical University Hospital (CSH-2010-C-016), Taiwan, ROC.

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Authors and Affiliations

  1. Department of Pathology, Chung-Shan Medical University Hospital and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan

    Wea-Lung Lin MS, DDS, Jeng-Dong Hsu MS, DDS & Chih-Ping Han MD, PhD

  2. Department of Internal Medicine, Armed-Force Hualien General Hospital, Hualien, Taiwan

    Wu-Hsien Kuo MD, PhD

  3. General Education Center, Central Taiwan University of Science and Technology, Taichung, Taiwan

    Wu-Hsien Kuo MD, PhD

  4. Division of Pediatric Cardiology, Department of Pediatrics, Chung Shan Medical University Hospital and School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Fong-Lin Chen MD, PhD

  5. Department of Statistics and Informatics Science, Providence University, Taichung, Taiwan

    Ming-Yung Lee PhD

  6. Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA

    Alexandra Ruan

  7. Department of Medical Imaging and Radiological Science, Chung-Shan Medical University, Department of Medical Imaging, Chung-Shan Medical University Hospital, Taichung, Taiwan

    Yeu-Sheng Tyan MD, PhD

  8. Taipei Institute of Pathology, Taipei, Taiwan

    Hung Chiang MD

  9. Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Taichung, Taiwan

    Chih-Ping Han MD, PhD

  10. Clinical Trial Center, Chung-Shan Medical University Hospital, Taichung, Taiwan

    Chih-Ping Han MD, PhD

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  1. Wea-Lung Lin MS, DDS
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  2. Wu-Hsien Kuo MD, PhD
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  3. Fong-Lin Chen MD, PhD
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  9. Chih-Ping Han MD, PhD
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Corresponding author

Correspondence to Chih-Ping Han MD, PhD.

Additional information

Epithelial ovarian cancer (EOC); Immunohistochemistry (IHC); Fluorescence in situ hybridization (FISH); Polymerase chain reaction (PCR); American Society of Clinical Oncology and the College of American Pathologists (ASCO-CAP)

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Lin, WL., Kuo, WH., Chen, FL. et al. Identification of the Coexisting HER2 Gene Amplification and Novel Mutations in the HER2 Protein-Overexpressed Mucinous Epithelial Ovarian Cancer. Ann Surg Oncol 18, 2388–2394 (2011). https://doi.org/10.1245/s10434-011-1572-z

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  • DOI: https://doi.org/10.1245/s10434-011-1572-z

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