Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2016 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2016 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer

  • Authors:
    • Ryuichi Wada
    • Soroku Yagihashi
    • Zenya Naito
  • View Affiliations / Copyright

    Affiliations: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113‑8602, Japan, Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan
    Copyright: © Wada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5104-5110
    |
    Published online on: October 26, 2016
       https://doi.org/10.3892/mmr.2016.5892
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Delta-human epidermal growth factor receptor 2 (HER2) is a splice variant of HER2, which lacks 16 amino acids in the extracellular domain. The aim of the present study was to elucidate the expression of delta‑HER2 and its clinicopathological correlation in Japanese patients with HER2‑overexpressing breast cancer. A total of 40 cases of HER2‑overexpressing breast cancer were investigated. The mRNA expression levels of wild type (wt)‑HER2 and delta‑HER2 were quantitated by quantitative polymerase chain reaction using RNA extracted from formalin‑fixed paraffin‑embedded specimens. In addition, the activated form of phosphorylated‑SRC (pSRC) and Ki‑67 were detected by immunostaining. The mRNA expression levels of wt‑HER2 varied largely, and the mRNA levels of delta‑HER2 were correlated with those of wt‑HER2. Furthermore, the enhanced immunostaining of pSRC was detected in 15 cases. Unsupervised hierarchal clustering of wt‑HER2, delta‑HER2 and pSRC was used to separate the cases into three clusters. In the first cluster, the levels of wt‑HER2 and delta‑HER2 were low, and pSRC immunostaining was low. Two other clusters were characterized by moderately and highly increased levels of wt‑HER2 and delta‑HER2 mRNA expression and enhanced pSRC. The delta/wt ratio was higher in the first cluster. Positive lymph node status and recurrence were more frequent in the first cluster compared with those in the two other clusters. Furthermore, the delta/wt ratio was significantly increased in lymph node‑positive and recurrent cases, compared with in lymph node‑negative and non‑recurrent cases. The present study demonstrated that delta-HER2 was expressed in Japanese patients with HER2‑overexpressing breast cancer. High mRNA expression levels of delta-HER2 were associated with pSRC and increased proliferation of tumor cells. A poor prognosis may be predicted by the increase in delta/wt ratio in HER2-overexpressing breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Barnard ME, Boeke CE and Tamimi RM: Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta. 1856:73–85. 2015.PubMed/NCBI

2 

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235:177–182. 1987. View Article : Google Scholar : PubMed/NCBI

4 

Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 98:10869–10874. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Lobbezoo DJ, van Kampen RJ, Voogd AC, Dercksen MW, van den Berkmortel F, Smilde TJ, van de Wouw AJ, Peters FP, van Riel JM, Peters NA, et al: Prognosis of metastatic breast cancer subtypes: The hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res Treat. 141:507–514. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Scott GK, Robles R, Park JW, Montgomery PA, Daniel J, Holmes WE, Lee J, Keller GA, Li WL, Fendly BM, et al: A truncated intracellular HER2/neu receptor produced by alternative RNA processing affects growth of human carcinoma cells. Mol Cell Biol. 13:2247–2257. 1993. View Article : Google Scholar : PubMed/NCBI

7 

Jackson C, Browell D, Gautrey H and Tyson-Capper A: Clinical significance of HER-2 splice variants in breast cancer progression and drug resistance. Int J Cell Biol. 2013:9735842013. View Article : Google Scholar : PubMed/NCBI

8 

Castiglioni F, Tagliabue E, Campiglio M, Pupa SM, Balsari A and Ménard S: Role of exon-16-deleted HER2 in breast carcinomas. Endocr Relat Cancer. 13:221–232. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Mitra D, Brumlik MJ, Okamgba SU, Zhu Y, Duplessis TT, Parvani JG, Lesko SM, Brogi E and Jones FE: An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance. Mol Cancer Ther. 8:2152–2162. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Kwong KY and Hung MC: A novel splice variant of HER2 with increased transformation activity. Mol Carcinog. 23:62–68. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Siegel PM, Ryan ED, Cardiff RD and Muller WJ: Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: Implications for human breast cancer. EMBO J. 18:2149–2164. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Alajati A, Sausgruber N, Aceto N, Duss S, Sarret S, Voshol H, Bonenfant D and Bentires-Alj M: Mammary tumor formation and metastasis evoked by a HER2 splice variant. Cancer Res. 73:5320–5327. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Marchini C, Gabrielli F, Iezzi M, Zenobi S, Montani M, Pietrella L, Kalogris C, Rossini A, Ciravolo V, Castagnoli L, et al: The human splice variant Δ16HER2 induces rapid tumor onset in a reporter transgenic mouse. PLoS One. 6:e187272011. View Article : Google Scholar : PubMed/NCBI

14 

Castagnoli L, Iezzi M, Ghedini GC, Ciravolo V, Marzano G, Lamolinara A, Zappasodi R, Gasparini P, Campiglio M, Amici A, et al: Activated d16HER2 homodimers and SRC kinase mediate optimal efficacy for trastuzumab. Cancer Res. 74:6248–6259. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lakhani SR, Ellis IO, Schnitt SJ, Tan PH and van de Vijver MJ: WHO Classification of tumours of the breast. IARC; Lyon: 2012

16 

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology/college of American pathologists clinical practice guideline update. J Clin Oncol. 31:3997–4013. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Allred DC, Harvey JM, Berardo M and Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 11:155–168. 1998.PubMed/NCBI

19 

Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, et al: Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med. 17:461–469. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Natori A, Hayashi N, Soejima K, Deshpande GA, Takahashi O, Cristofanilli M, Ueno NT and Yamauchi H: A comparison of epidemiology, biology, and prognosis of inflammatory breast cancer in Japanese and US populations. Clin Breast Cancer. 13:460–464. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Bianchini G and Gianni L: The immune system and response to HER2-targeted treatment in breast cancer. Lancet Oncol. 15:e58–e68. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wada R, Yagihashi S and Naito Z: mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer. Mol Med Rep 14: 5104-5110, 2016.
APA
Wada, R., Yagihashi, S., & Naito, Z. (2016). mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer. Molecular Medicine Reports, 14, 5104-5110. https://doi.org/10.3892/mmr.2016.5892
MLA
Wada, R., Yagihashi, S., Naito, Z."mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer". Molecular Medicine Reports 14.6 (2016): 5104-5110.
Chicago
Wada, R., Yagihashi, S., Naito, Z."mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer". Molecular Medicine Reports 14, no. 6 (2016): 5104-5110. https://doi.org/10.3892/mmr.2016.5892
Copy and paste a formatted citation
x
Spandidos Publications style
Wada R, Yagihashi S and Naito Z: mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer. Mol Med Rep 14: 5104-5110, 2016.
APA
Wada, R., Yagihashi, S., & Naito, Z. (2016). mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer. Molecular Medicine Reports, 14, 5104-5110. https://doi.org/10.3892/mmr.2016.5892
MLA
Wada, R., Yagihashi, S., Naito, Z."mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer". Molecular Medicine Reports 14.6 (2016): 5104-5110.
Chicago
Wada, R., Yagihashi, S., Naito, Z."mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer". Molecular Medicine Reports 14, no. 6 (2016): 5104-5110. https://doi.org/10.3892/mmr.2016.5892
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team