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Epidermal Growth Factor Receptor (EGFR) Expression is Associated With a Worse Prognosis in Gastric Cancer Patients Undergoing Curative Surgery

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Abstract

Background

In gastric cancer, the recurrence rate is high even after curative surgery. A relevant issue is the identification of independent prognostic factors to select high-risk patients; such features can be used as predictive factors for tailored therapies. In this study we have investigated the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for predicting cancer behavior and clinical outcome in gastric cancer patients undergoing potentially curative surgery.

Methods

Epidermal growth factor receptor determination using a commercially available immunohistochemistry (IHC) kit was performed in tissues from 82 gastric cancer patients receiving primary surgical treatment and in 25 normal gastric mucosa specimens from noncancer patients. The EGFR positivity was correlated with disease recurrence and survival in univariate and multivariate analyses.

Results

Forty-four percent (36 cases) of gastric cancers were EGFR positive. In 66 curatively treated patients, EGFR expression correlated with disease recurrence and poorer survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, advanced tumor extension (T3 or T4), nodal metastases, and EGFR expression were the only independent covariates. In particular, EGFR expression was shown to be a significant predictor of poor prognosis among gastric cancer patients having the same stage according to the current TNM staging system.

Conclusions

These findings suggest that EGFR expression may be useful in identifying high-risk gastric cancer patients undergoing potentially curative surgery. Multimodal treatments should be considered in the adjuvant treatment of these patients.

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References

  1. Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130

    Article  PubMed  Google Scholar 

  2. Hartgrink HH, van de Velde CJ (2005) Status of extended lymph node dissection: locoregional control is the only way to survive gastric cancer: J Surg Oncol 90:153–165

    Article  PubMed  Google Scholar 

  3. Novotny AR, Schuhmaker C, Bush R, et al. (2006) Predicting individual survival after gastric cancer resection: validation of a U.S.-derived nomogram at a single high-volume center in Europe. Ann Surg 243:74–81

    Article  PubMed  Google Scholar 

  4. Ajani JA, Mansfield PF, Crane CH, et al. (2005) Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol 23:1237–1244

    Article  PubMed  CAS  Google Scholar 

  5. Allal AS, Zwahlen D, Brundler MA, et al. (2005) Neoadjuvant radiochemotherapy for locally advanced gastric cancer: long-term results of a phase I trial. Int J Radiat Oncol Biol Phys 63:1286–1289

    Article  PubMed  Google Scholar 

  6. MacDonald JS (2005) Role of post-operative chemoradiation in resected gastric cancer. J Surg Oncol 90:166–170

    Article  PubMed  Google Scholar 

  7. Kim S, Lim do H, Lee J, et al. (2005) An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 63:1279–285

    Article  PubMed  Google Scholar 

  8. Allum W, Cunningham D, Weeden S, et al. (2003) Perioperative chemotherapy in operable gastric and lower oesophageal cancer: a randomized, controlled trial (the MAGIC trial, ISRCTN 93793971) [Abstract #998], Proc ASCO 22:249a

  9. Chong G, Cunningham D (2005) Gastrointestinal cancer: recent developments in medical oncology. Eur J Surg Oncol 31:453–460

    Article  PubMed  CAS  Google Scholar 

  10. Leong T (2004) Evolving role of chemoradiation in the adjuvant treatment of gastric cancer. Expert Rev Anticancer Ther 4:585–594

    Article  PubMed  CAS  Google Scholar 

  11. Stahl M (2004) Adjuvant chemoradiotherapy in gastric cancer and carcinoma of the oesophago-gastric junction. Onkologie 27:33–36

    Article  PubMed  CAS  Google Scholar 

  12. Hartgrink HH, van de Velde CJ, Putter H, et al. (2004) Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch Gastric Cancer Group Trial. J Clin Oncol 22:2069–2077

    Article  PubMed  CAS  Google Scholar 

  13. Hundahl SA, Wanebo HJ (2005) Changing gastric cancer treatment in the United States and the pursuit of quality. Eur J Surg Oncol 31:605–615

    Article  PubMed  CAS  Google Scholar 

  14. Falcone A (2003) Future strategies and adjuvant treatment of gastric cancer. Ann Oncol 14:45–47

    Article  Google Scholar 

  15. Roukos DH, Kappas AM (2005) Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol 2:98–107

    Article  PubMed  Google Scholar 

  16. Wagner AD, Grothe W, Haerting J, et al. (2006) Chemotherapy in advanced gastric cancer: a systematic review and a meta-analysis based on aggregate data. J Clin Oncol 24:2903–2909

    Article  PubMed  CAS  Google Scholar 

  17. Sutter AP, Zeitz M, Scherübl H (2004) Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer. Onkologie 27:17–21

    Article  PubMed  CAS  Google Scholar 

  18. Galizia G, Ferraraccio F, Lieto E, et al. (2006) p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate. J Surg Oncol 93:241–252

    Article  PubMed  CAS  Google Scholar 

  19. Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003;21:2787–2799

    Article  PubMed  CAS  Google Scholar 

  20. Garcia I, Vizoso F, Martin A, et al. (2003) Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol 10:234–241

    Article  PubMed  CAS  Google Scholar 

  21. Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445–2459

    Article  PubMed  CAS  Google Scholar 

  22. Grunwald V, Hidalgo M (2003) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95:851–867

    Article  PubMed  Google Scholar 

  23. Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7:2958–2970

    PubMed  CAS  Google Scholar 

  24. Galizia G, Lieto E, Ferrarraccio F, et al. (2006) Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann Surg Oncol 13:823–835

    Article  PubMed  Google Scholar 

  25. Kopp R, Rothbauer E, Ruge M, et al. (2003) Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res 162:115–132

    PubMed  CAS  Google Scholar 

  26. Gamboa-Dominguez A, Dominguez-Fonseca C, Quintanilla-Martinez L, et al. (2004) Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system. Mod Pathol 17:579–587

    Article  PubMed  CAS  Google Scholar 

  27. Ito R, Nakayama H, Yoshida K, et al. (2004) Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma. Virchows Arch 444:324–331

    Article  PubMed  CAS  Google Scholar 

  28. Grogg KL, Lohse CM, Pankratz VS, et al. (2003) Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival. Mod Pathol 16:641–651

    Article  PubMed  Google Scholar 

  29. Hiyama T, Tanaka S, Yoshihara M, et al. (2004) Chromosomal and microsatellite instability in sporadic gastric cancer. J Gastroenterol Hepatol 19:756–760

    Article  PubMed  CAS  Google Scholar 

  30. Kalbfleisch JD, Prentice RL (1980) The Statistical Analysis of Failure Time Data. New York, Wiley

    Google Scholar 

  31. Santoro E, Carboni M, Catarci M, et al. (1997) DNA ploidy, proliferative index and EGF-R status in 130 cases of resected gastric cancer: a multivariate analysis. Hepatogastroenterology 44:826–837

    PubMed  CAS  Google Scholar 

  32. Hirono Y, Tsugawa K, Fushida S, et al. (1995) Amplification of epidermal growth factor receptor gene and its relationship to survival in human gastric cancer. Oncology 52:182–188

    Article  PubMed  CAS  Google Scholar 

  33. Sanz-Ortega J, Steinberg SM, Moro E, et al. (2000) Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer. Histol Histopathol 15:455–462

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Surgical Oncology, “F. Magrassi - A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico, Edificio 17, Via Pansini, 5, 80131, Naples, Italy

    Gennaro Galizia, Eva Lieto, Paolo Castellano, Vincenzo Imperatore, Margherita Pinto & Anna Zamboli

  2. Division of Medical Oncology, “F. Magrassi - A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico, Edificio 17, Via Pansini, 5, 80131, Naples, Italy

    Michele Orditura & Ferdinando De Vita

  3. Division of Pathology, “F. Magrassi - A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico, Edificio 17, Via Pansini, 5, 80131, Naples, Italy

    Anna La Mura & Francesca Ferraraccio

Authors
  1. Gennaro Galizia
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  2. Eva Lieto
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  3. Michele Orditura
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  4. Paolo Castellano
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  5. Anna La Mura
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  6. Vincenzo Imperatore
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  7. Margherita Pinto
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  8. Anna Zamboli
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  9. Ferdinando De Vita
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  10. Francesca Ferraraccio
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Correspondence to Gennaro Galizia.

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Galizia, G., Lieto, E., Orditura, M. et al. Epidermal Growth Factor Receptor (EGFR) Expression is Associated With a Worse Prognosis in Gastric Cancer Patients Undergoing Curative Surgery. World J Surg 31, 1458–1468 (2007). https://doi.org/10.1007/s00268-007-9016-4

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  • DOI: https://doi.org/10.1007/s00268-007-9016-4

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