Skip to main content

Advertisement

Log in

Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The HER2 gene, which is located on chromosomes 17, is a therapeutic target for cancer. Amplification of HER2 has been described in several tumor types. However, few studies of HER2 gene amplification and protein expression in esophageal carcinoma have been conducted. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics, including survival rate, of esophageal squamous carcinoma. The clinical data of 145 patients admitted in Renmin Hospital of Wuhan University, from 2000 to 2005, were reviewed. The HER2 protein expression and gene status in 145 esophageal carcinomas were evaluated using immunohistochemistry and fluorescence in situ hybridization. The survival rate was calculated by the Kaplan–Meier method and the log-rank test using SPSS13.0 software. Compared to normal esophageal epithelium (23/95, 24.2%), HER2 protein was overexpressed in most esophageal squamous carcinoma tissues (60/145, 41.4%), of which 45 (31.0%) were 2+ and 15 (10.4%) were 3+, HER2 overexpression associated significantly with HER2 gene amplification. There is a correlation between the overexpression of HER2 and the differentiation of the carcinoma, the HER2 gene amplification and the differentiation of the carcinoma and the tumor stage. According to univariate analysis, there was a significant difference in survival rates when cases with and without HER-2/neu overexpression or amplification were compared. HER-2/neu amplification/overexpression may be used as an independent prognostic factor in patients with esophageal squamous cancer, and patients with HER-2/neu amplification/overexpression might be potential candidates for new adjuvant therapies that involve the use of humanized monoclonal antibodies.

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

Access this article

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

References

  1. Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998;83(10):2049–53.

    Article  PubMed  CAS  Google Scholar 

  2. Mascarello JT, Brothman AR, Davison K, Dewald GW, Herrman M, McCandless D, Park JP, Persons DL, Rao KW, Schneider NR, Vance GH, Cooley LD. Proficiency testing for laboratories performing fluorescence in situ hybridization with chromosome-specific DNA probes. Arch Pathol Lab Med. 2002;126(12):1458.

    PubMed  CAS  Google Scholar 

  3. Corley DA, Buffler PA. Oesophageal and gastric cardia adenocarcinoma: analysis of regional variation using the Cancer Incidence in FIVE Continents database. Int J Epidemiol. 2001;30(6):1415–25.

    Article  PubMed  CAS  Google Scholar 

  4. Takehana T, Kunitomo K, Kono K, Kitahara F, Iizuka H, Matsumoto Y, Fujino MA, Ooi A. Status of c-ERBB-2 in gastric adenocarcinoma:a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immunosorbent assay. Int J Cancer. 2002;98(6):833–7.

    Article  PubMed  CAS  Google Scholar 

  5. Konecny G, Pauletti G, Pegram M, Untch M, Dandekar S, Aguilar Z, Wilson C, Rong HM, Bauerfeind I, Felber M, Wang HJ, Bery M, Seshadri R, Hepp H, Slamon DJ. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95(2):142–53.

    Article  PubMed  CAS  Google Scholar 

  6. Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.

    Article  PubMed  CAS  Google Scholar 

  7. Penault-Llorca F, Vincent-Salomon A, Mathieu MC, Trillet-Lenoir V, Khayat D, Marty M. Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer (MBC). J Clin Oncol (Meeting Abstracts). 2005;23:69s. Abstract 764.

    Google Scholar 

  8. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.

    Article  PubMed  CAS  Google Scholar 

  9. Révillion F, Bonneterre J, Peyrat JP. ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer. 1998;34(6):791–808.

    Article  PubMed  Google Scholar 

  10. Sato-Kuwabara Y, Neves JI, Fregnani JHTG, Sallum RA, Soares FA. Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and Immunohistochemistry. BMC Cancer. 2009;9(6):1207–471.

    Google Scholar 

  11. Mimura K, Kono K, Hanawa M, Mitsui F, Sugai H, Miyagawa N, Ooi A, Fujii H. Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma. Br J Cancer. 2005;92(7):1253–60.

    Article  PubMed  CAS  Google Scholar 

  12. Reichelt U, Duesedau P, Tsourlakis MC, Quaas A, Link BC, Schurr PG, Kaifi JT, Gros SJ, Yekebas EF, Marx A, Simon R, Izbicki JR, Sauter G. Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol. 2007;20(1):120–9.

    Article  PubMed  CAS  Google Scholar 

  13. Sunpaweravong P, Sunpaweravong S, Puttawibul P, Mitarnun W, Zeng C, Baron AE, Franklin W, Said S, Varella-Garcia M. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2005;131(2):111–9.

    Article  PubMed  CAS  Google Scholar 

  14. Friess H, Fukuda A, Tang WH, Eichenberger A, Furlan N, Zimmermann A, Korc M, Buchler MW. Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer:overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. World J Surg. 1999;23(10):1010–8.

    Article  PubMed  CAS  Google Scholar 

  15. Suzuki H, Abo S, Kitamura M, Hashimoto M, Izumi K, Terada K, Sugiyama T. Gene amplification of int-2 and erbB in human esophageal cancer: relationship to clinicopathological variables. Cancer Invest. 1997;15(5):411–15.

    Article  PubMed  CAS  Google Scholar 

  16. Wells A. EGF receptor. Int J Biochem Cell Biol. 1999;31(6):637–43.

    Article  PubMed  CAS  Google Scholar 

  17. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.

    Article  PubMed  CAS  Google Scholar 

  18. Hardwick RH, Barham CP, Ozua P, Newcomb PV, Savage P, Powell R, Rahamin J, Alderson D. Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis. Eur J Surg Oncol. 1997;23(1):30–5.

    Article  PubMed  CAS  Google Scholar 

  19. Lam KY, Tin L, Ma L. C-erbB-2 protein expression in oesophageal squamous epithelium from oesophageal squamous cell carcinomas, with special reference to histological grade of carcinoma and pre-invasive lesions. Eur J Surg Oncol. 1998;24(5):431–5.

    Article  PubMed  CAS  Google Scholar 

  20. Dreilich M, Wanders A, Brattstrom D, Bergstrom S, Hesselius P, Wagenius G. Bergqvist M: HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival. Dis Esophagus. 2006;19(4):224–31.

    Article  PubMed  CAS  Google Scholar 

  21. Suo Z, Su W, Holm R, Nesland JM. Lack of expression of c-erbB-2 oncoprotein in human esophageal squamous cell carcinomas. Anticancer Res. 1995;15(6B):2797–8.

    PubMed  CAS  Google Scholar 

  22. Suwanagool P, Parichatikanond P. Maeda S: Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study. Asian Pac J Allergy Immunol. 1993;11(2):119–22.

    PubMed  CAS  Google Scholar 

  23. Dreilich M, Wanders A, Brattström D, Bergström S, Hesselius P, Wagenius G, Bergqvist M. HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival. Dis Esophagus. 2006;19(4):224–31.

    Article  PubMed  CAS  Google Scholar 

  24. Hofmann M, Stoss O, Gaiser T, Kneitz H, Heinmoller P, Gutjahr T, Kaufmann M, Henkel T, Ruschoff J. Central HER2 IHC and FISH analysis in a trastuzumab [Herceptin (R)] Phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J Clin Pathol. 2008;61(1):89–94.

    Article  PubMed  CAS  Google Scholar 

  25. Varis A, Zaika A, Puolakkainen P, Nagy B, Madrigal I, Kollola A, Väyrynen A, Kärkkäinen P, Moskaluk C, El-Rifai W, Knuutila S. Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer. 2004;109(4):548–53.

    Article  PubMed  CAS  Google Scholar 

  26. Wang S, Hossein Saboorian MH, Frenkel EP, Haley BB, Siddiqui MT, Gokaslan S, Hynan L. Ashfaq R: Aneusomy 17 in breast cancer: Its role in Her2/neu protein expression and implication for clinical assessment of Her-2/neu status. Mod Pathol. 2002;15(2):137–45.

    Article  PubMed  Google Scholar 

  27. Seidal T, Balaton AJ, Battifora H. Interpretation and quantification of immunostains. Am J Surg Pathol. 2001;25(9):1204–7.

    Article  PubMed  CAS  Google Scholar 

  28. Pauletti G, Godolphin W, Press MF, Slamon DJ. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene. 1996;13(1):63–72.

    PubMed  CAS  Google Scholar 

  29. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI, Yoo CH, Son BH, Cho EY, Chae SW, Kim EJ, Sohn JH, Ryu SH, Sepulveda AR. HER-2/neu Amplification Is an Independent Prognostic Factor in Gastric Cancer. Dig Dis Sci. 2006;51(8):1371–9.

    Article  PubMed  CAS  Google Scholar 

  30. Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005;97(9):643–55.

    Article  PubMed  CAS  Google Scholar 

  31. Cappuzzo F, Varella-Garcia M, Shigematsu H, Domenichini I, Ceresoli GL, Bartolini S, Rossi E, Ludovini V, Gregorc V, Toschi L, Franklin WA, Crino L, Gazdar AF, Bunn PA Jr, Hirsch FR. Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive nonsmall-cell lung cancer patients. J Clin Oncol. 2005;23(22):5007–18.

    Article  PubMed  CAS  Google Scholar 

  32. Tsuda H. HER-2 (c-erbB-2) test update: present status and problems. Br Cancer. 2006;13(3):236–48.

    Article  Google Scholar 

  33. Baselga J. The EGFR as a target for anticancer therapy-focus on cetuximab. Eur J Cancer. 2001;37(Suppl 4):S16–22.

    Article  PubMed  CAS  Google Scholar 

  34. Leyland-Jones B. Trastuzumab: hopes and realities. Lancet Oncol. 2002;3(3):137–44.

    Article  PubMed  CAS  Google Scholar 

  35. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol. 2004;22(6):1063–70.

    Article  PubMed  CAS  Google Scholar 

  36. Tuma RS. Trastuzumab trials steal show at ASCO meeting. J Natl Cancer Inst. 2005;97(12):870–1.

    Article  PubMed  Google Scholar 

  37. Kawaguchi Y, Kono K, Mimura K, Mitsui F, Sugai H, Akaike H, Fujii H. Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma. Br J Cancer. 2007;97(4):494–501.

    Article  PubMed  CAS  Google Scholar 

  38. Gros SJ, Kurschat N, Dohrmann T, Reichelt U, Dancau AM, Peldschus K, Adam G, Hoffman RM, Izbicki JR, Kaifi JT. Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma. Mol Cancer Ther. 2010;9(7):2037–45.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Mr. Guo-sheng Xiong and Mis. Hong Hu for providing technical assistance, Dr. Ya-bing Huang and Dr. Lin Liu for assistance in standardizing the FISH protocol, Dr. Xiao-fan Li for revising this article.

Conflict of interests

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei-Guo Dong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhan, N., Dong, WG., Tang, YF. et al. Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma. Med Oncol 29, 933–940 (2012). https://doi.org/10.1007/s12032-011-9850-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9850-y

Keywords

Navigation