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Open Access 01-12-2015 | Research article

The prognostic value of EGFR overexpression and amplification in Esophageal squamous cell Carcinoma

Authors: Dongxian Jiang, Xiaojing Li, Haixing Wang, Yuan Shi, Chen Xu, Shaohua Lu, Jie Huang, Yifan Xu, Haiying Zeng, Jieakesu Su, Yingyong Hou, Lijie Tan

Published in: BMC Cancer | Issue 1/2015

Abstract

Background

In view of the prominent role in cancer cell biology and alteration in substantial numbers of ESCC, defining EGFR molecular characteristics relevant to patient prognosis is of great importance. Therefore, we analyzed the protein expression and gene copy variation of the epithelial growth factor receptor (EGFR) in Chinese esophageal squamous cell carcinoma (ESCC) and explored the possible associations with various features of the tumors and survival of the patients.

Methods

Sections were made from tissue microarray composed of 96 ESCC, and examined for EGFR expression by means of immunohistochemistry (IHC) and for EGFR gene amplification by means of fluorescence in situ hybridization (FISH). The results of IHC were evaluated with six different reported scoring systems. Correlation with clinical features and survival was evaluated using chi-square test and Kaplan–Meier analysis.

Results

EGFR overexpression according to scoring system 1 significantly correlated with advanced lymph node involvement (P = 0.046), patient disease specific free survival (DFS) (P = 0.006) and overall survival (OS) (P = 0.007). No such association was observed using other 5 scoring systems (P > 0.05 ). EGFR amplification was associated with lymph node metastasis (P = 0.028), but not correlated with DFS and OS until 20 months.

Conclusions

EGFR IHC overexpression evaluated by scoring system 1 might be suitable to be used in predicting patients survival in ESCC. EGFR gene amplification showed delayed prognostic information after 20 months.

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Montgomery EF, Boffetta P, Daigo Y, Shimizu M, Shimoda T. WHO classification of tumors of the oesophagus. 4th ed. Lyon: IARC Press; 2010.

Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381:400–12.CrossRefPubMed

Dipetrillo T, Suntharalingam M, Ng T, Fontaine J, Horiba N, Oldenburg N, et al. Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial. Am J Clin Oncol. 2012;35:64–7.CrossRefPubMed

Jatoi A, Soori G, Foster NR, Hiatt BK, Knost JA, Fitch TR, et al. Phase II study of preoperative pemetrexed, carboplatin, and radiation followed by surgery for locally advanced esophageal cancer and gastroesophageal junction tumors. J Thorac Oncol. 1994;2010:5.

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge HM, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;2074–2084:366.

Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, et al. Popescu R:Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009;20:1522–8.CrossRefPubMed

Ahmed S, Sami A, Xiang J. HER2-directed therapy: current treatment options for HER2-positive breast cancer. Breast Cancer. 2015;22:101–16.CrossRefPubMed

Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.CrossRefPubMed

Sanford M, Scott LJ. Imatinib: as adjuvant therapy for gastrointestinal stromal tumour. Drugs. 2010;70:1963–72.CrossRefPubMed

10.

Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013;14:627–37.CrossRefPubMed

11.

Fichter CD, Timme S, Braun JA, Gudernatsch V, Schopflin A, Bogatyreva L, et al. EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer. Int J Cancer. 2014;135:1517–30.CrossRefPubMed

12.

Wei QC, Chen LR, Sheng LM, Nordgren H, Wester K, Carlsson J. EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. Int J Oncol. 2007;31:493–9.PubMed

13.

Hanawa M, Suzuki S, Dobashi Y, Yamane T, Kono K, Enomoto N, et al. EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer. 2006;118:1173–80.CrossRefPubMed

14.

Gibault L, Metges JP, Conan-Charlet V, Lozac'H P, Robaszkiewicz M, Bessaguet C, et al. Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer. 2005;93:107–15.CrossRefPubMedPubMedCentral

15.

Itakura Y, Sasano H, Shiga C, Furukawa Y, Shiga K, Mori S, et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification. Cancer. 1994;74:795–804.CrossRefPubMed

16.

Kato H, Arao T, Matsumoto K, Fujita Y, Kimura H, Hayashi H, et al. Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma. Int J Oncol. 2013;42:1151–8.PubMedPubMedCentral

17.

Sunpaweravong P, Sunpaweravong S, Puttawibul P, Mitarnun W, Zeng C, Baron AE, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2005;131:111–9.CrossRefPubMed

18.

Kitagawa Y, Ueda M, Ando N, Ozawa S, Shimizu N, Kitajima M. Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 1996;2:909–14.PubMed

19.

Kaifi JT, Gusani NJ, Jiang Y, Mackley HB, Dye CE, Mathew A, et al. Multidisciplinary management of early and locally advanced esophageal cancer. J Clin Gastroenterol. 2011;45:391–9.CrossRefPubMed

20.

Shi Y, He D, Hou Y, Hu Q, Xu C, Liu Y, et al. An alternative high output tissue microarray technique. Diagn Pathol. 2013;8:9.CrossRefPubMedPubMedCentral

21.

Hirsch FR, Varella-Garcia M, Bunn PJ, Di Maria MV, Veve R, Bremmes RM, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21:3798–807.CrossRefPubMed

22.

Cronin J, McAdam E, Danikas A, Tselepis C, Griffiths P, Baxter J, et al. Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus (BE). Am J Gastroenterology. 2011;106:46–56.CrossRef

23.

Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012;13:33–42.CrossRefPubMed

24.

Yang YL, Xu KL, Zhou Y, Gao X, Chen LR. Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas. Chin Med J (Engl). 2012;125:450–4.

25.

Grobe A, Eichhorn W, Fraederich M, Kluwe L, Vashist Y, Wikner J, et al. Immunohistochemical and FISH analysis of EGFR and its prognostic value in patients with oral squamous cell carcinoma. J Oral Pathol Med. 2014;43:205–10.CrossRefPubMed

26.

Zhang J, Jiang D, Li X, Lv J, Xie L, Zheng L, et al. Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery. Lab Investig. 2014;94:917–26.CrossRefPubMed

27.

Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005;97:643–55.CrossRefPubMed

28.

Hou J, Jiang DX, Zhang JC, Gavine PR, Xu ST, Liu YL, et al. Frequency, characterization, and prognostic analysis of PIK3CA gene mutations in Chinese esophageal squamous cell carcinoma. Hum Pathol. 2014;45:352–8.CrossRefPubMed

29.

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

30.

Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9:154–62.CrossRefPubMedPubMedCentral

31.

Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 2012;22:2109–19.CrossRefPubMedPubMedCentral

32.

Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer. 2006;6:714–27.CrossRefPubMed

33.

Gonzaga IM, Soares-Lima SC, de Santos PT, Blanco TC, de Reis BS, Quintella DC, et al. Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas. BMC Cancer. 2012;12:569.CrossRefPubMedPubMedCentral

34.

Abedi-Ardekani B, Dar NA, Mir MM, Zargar SA, Lone MM, Martel-Planche G, et al. Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia. BMC Cancer. 2012;12:602.CrossRefPubMedPubMedCentral

Title: The prognostic value of EGFR overexpression and amplification in Esophageal squamous cell Carcinoma
Authors: Dongxian Jiang
Xiaojing Li
Haixing Wang
Yuan Shi
Chen Xu
Shaohua Lu
Jie Huang
Yifan Xu
Haiying Zeng
Jieakesu Su
Yingyong Hou
Lijie Tan
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-015-1393-8

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