Skip to main content

Advertisement

SpringerLink
Log in

Expression and association of HER2 with prognosis in early-stage (T1–T2N0M0) non-small cell lung cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

The expression of human epidermal growth factor receptor 2 (HER2) is related to tumor progression in many human malignancies. This study evaluated the significance of HER2 in early-stage non-small cell lung cancer (NSCLC). Specimens were obtained from 172 patients with early-stage (T1–T2N0M0) NSCLC, which included T1N0M0 (n = 52) and T2N0M0 (n = 120). The expression of HER2 was determined by immunohistochemistry (IHC). HER2 expression and its relationship with clinicopathological parameters and survival were analyzed. The expression of HER2 was significantly higher in the non-squamous cell carcinoma than in the squamous cell carcinoma (74.3 % vs. 53.7 %, p = 0.008). HER2 expression and tumor size were independent prognostic indicators in the multivariate analysis (p = 0.007 and p = 0.015, respectively). Expression of HER2 indicated a worse 5-year overall survival (65 % vs. 86 %, p = 0.014), especially for stages IB and IIA diseases (p = 0.035 and p = 0.043, respectively) and adenocarcinoma (p = 0.047). Therefore, HER2 may be related with the pathogenesis of NSCLC and act as an unfavorable prognostic factor in T1N0M0 and T2N0M0 NSCLC, especially in stages IB and IIA diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HER2:

Human epidermal growth factor receptor 2

NSCLC:

Non-small cell lung cancer

IHC:

Immunohistochemistry

ROC:

Receiver operating characteristic

OS:

Overall survival

AUC:

Area under the ROC curve

ORR:

Overall response rate

TTP:

Time to progression

References

  1. Carney DN. Lung cancer–time to move on from chemotherapy. N Engl J Med. 2002;346:126–8.

    Article  PubMed  Google Scholar 

  2. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.

    Article  PubMed  Google Scholar 

  3. Paesmans M, Sculier JP, Libert P, et al. Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European lung cancer working party. J Clin Oncol. 1995;13:1221–30.

    CAS  PubMed  Google Scholar 

  4. Metro G, Crinò L. Advances on EGFR mutation for lung cancer. Transl Lung Cancer Res. 2012;1:5–13.

    PubMed  PubMed Central  Google Scholar 

  5. Situ D, Wang J, Shao W, Zhu ZH. Assessment and treatment of cancer pain: from Western to Eastern. Ann Palliat Med. 2012;1:32–44.

    PubMed  Google Scholar 

  6. Kaptain S, Tan LK, Chen B. Her-2/neu and breast cancer. Diagn Mol Pathol. 2001;10:139–52.

    Article  CAS  PubMed  Google Scholar 

  7. Schuell B, Gruenberger T, Scheithauer W, et al. HER 2/neu protein expression in colorectal cancer. BMC Cancer. 2006;6:123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brabender J, Danenberg KD, Metzger R, et al. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer is correlated with survival. Clin Cancer Res. 2001;7:1850–5.

    CAS  PubMed  Google Scholar 

  9. Smith HS. Painful boney metastases. Ann Palliat Med. 2012;1:14–31.

    PubMed  Google Scholar 

  10. Mimura K, Kono K, Hanawa M, et al. Frequencies of HER2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma. Br J Cancer. 2005;92:1253–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Noguchi M, Murakami M, Bennett W, et al. Biological consequences of overexpression of a transfected HER2 gene in immortalized human bronchial epithelial cells. Cancer Res. 1993;53:2035–43.

    CAS  PubMed  Google Scholar 

  12. Yu D, Wang SS, Dulski KM, et al. HER2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res. 1994;54:3260–6.

    CAS  PubMed  Google Scholar 

  13. Cox G, Jones J, Andi A, et al. A biological staging model for operable non-small cell lung cancer. Thorax. 2001;56:561–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Carbognani P, Tincani G, Crafa P, et al. Biological markers in non-small cell lung cancer. Retrospective study of 10-year follow-up after surgery. J Cardiovasc Surg (Torino). 2002;43:545–8.

    CAS  Google Scholar 

  15. Kuyama S, Hotta K, Tabata M, et al. Impact of HER2 gene and protein status on the treatment outcome of cisplatin-based chemoradiotherapy for locally advanced non-small cell lung cancer. J Thorac Oncol. 2008;3:477–82.

    Article  PubMed  Google Scholar 

  16. Korrapati V, Gaffney M, Larsson LG, et al. Effect of HER2/neu expression on survival in non-small-cell lung cancer. Clin Lung Cancer. 2001;2:216–9.

    Article  CAS  PubMed  Google Scholar 

  17. Szelachowska J, Jelen M, Kornafel J. Prognostic significance of intracellular laminin and Her2/neu overexpression in non-small cell lung cancer. Anticancer Res. 2006;26:3871–6.

    CAS  PubMed  Google Scholar 

  18. Selvaggi G, Scagliotti GV, Torri V, et al. HER2/neu overexpression in patients with radically resected non small cell lung carcinoma. Impact on long-term survival. Cancer. 2002;94:2669–74.

    Article  PubMed  Google Scholar 

  19. Tan D, Deeb G, Wang J, et al. HER2/neu protein expression and gene alteration in stage I–IIIA non-small-cell lung cancer: A study of 140 cases using a combination of high throughput tissue microarray, immunohistochemistry, and fluorescent in situ hybridization. Diagn Mol Pathol. 2003;12:201–11.

    Article  CAS  PubMed  Google Scholar 

  20. Greatens TM, Niehans GA, Rubins JB, et al. Do molecular markers predict survival in non-small-cell lung cancer? Am J Respir Crit Care Med. 1998;157:1093–7.

    Article  CAS  PubMed  Google Scholar 

  21. Toh CK, Ahmad B, Soong R, et al. Correlation between epidermal growth factor receptor mutations and expression of female hormone receptors in East-Asian lung adenocarcinomas. J Thorac Oncol. 2010;5:17–22.

    Article  PubMed  Google Scholar 

  22. Pelosi G, Del Curto B, Dell’Orto P, et al. Lack of prognostic implications of HER2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I–III neuroendocrine tumours (NET) of the Lung. Int J Cancer. 2005;113:101–8.

    Article  CAS  PubMed  Google Scholar 

  23. Xu JM, Han Y, Duan HQ, et al. EGFR mutations and HER2/3 protein expression and clinical outcome in Chinese advanced non-small cell lung cancer patients treated with Gefitinib. J Cancer Res Clin Oncol. 2009;135:771–82.

    Article  CAS  PubMed  Google Scholar 

  24. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350:379–92.

    Article  CAS  PubMed  Google Scholar 

  25. Liu L, Shao X, Gao W, et al. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: a meta-analysis of published data. J Thorac Oncol. 2010;5:1922–32.

    Article  PubMed  Google Scholar 

  26. Takenaka M, Hanagiri T, Shinohara S, et al. The prognostic significance of her2 overexpression in non-small cell lung cancer. Anticancer Res. 2011;31:4631–6.

    PubMed  Google Scholar 

  27. Kern JA, Schwartz DA, Nordberg JE, et al. p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res. 1990;50:5184–7.

    CAS  PubMed  Google Scholar 

  28. Weiner DB, Nordberg J, Robinson R, et al. Expression of the neu gene-encoded protein (p185neu) in human non-small cell carcinomas of the lung. Cancer Res. 1990;50:421–5.

    CAS  PubMed  Google Scholar 

  29. Awaya H, Takeshima Y, Furonaka O, et al. Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung. J Clin Pathol. 2005;58:1076–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ochiai A, Akimoto S, Kanai Y, et al. c-erbB-2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun. 1994;205:73–8.

    Article  CAS  PubMed  Google Scholar 

  31. Giatromanolaki A, Koukourakis MI, O’Byrne K, et al. Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. Anticancer Res. 1999;16:3819–25.

    Google Scholar 

Download references

Acknowledgments

This study was supported by the Fundamental Research Funds for the Central Universities and the grant from Youth Training Plan of Sun Yat-Sen University (No. 10ykpy38), the Research Award Fund for Outstanding Young Researchers in Sun Yat-Sen Cancer Center (Nos. 303045172006 and 303045172005), the National Natural Science Foundation of China (No. 30901728) and the Science & Technology Pillar Program of Guangdong Province (No. 2011B031800220). The authors declare their independence of sponsors, and the content of this article has not been influenced by the sponsors.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Qing Xia, Ningning Zhou & Wenqi Jang

  2. State Key Laboratory of Oncology in South China, Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Zhihua Zhu & Dongrong Situ

  3. State Key Laboratory of Oncology in South China, Department of Anesthesia, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Jian Wang

Authors
  1. Qing Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhihua Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongrong Situ
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ningning Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenqi Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhihua Zhu or Ningning Zhou.

Additional information

Xia Zhu and Wang contributed equally to this article

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xia, Q., Zhu, Z., Wang, J. et al. Expression and association of HER2 with prognosis in early-stage (T1–T2N0M0) non-small cell lung cancer. Tumor Biol. 33, 1719–1725 (2012). https://doi.org/10.1007/s13277-012-0429-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0429-9

Keywords

Search

Navigation