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Erschienen in: World Journal of Surgery 7/2007

01.07.2007

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

verfasst von: Gennaro Galizia, Eva Lieto, Michele Orditura, Paolo Castellano, Anna La Mura, Vincenzo Imperatore, Margherita Pinto, Anna Zamboli, Ferdinando De Vita, Francesca Ferraraccio

Erschienen in: World Journal of Surgery | Ausgabe 7/2007

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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.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef
2.
Zurück zum Zitat 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 90:153–165PubMedCrossRef 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 90:153–165PubMedCrossRef
3.
Zurück zum Zitat 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 243:74–81PubMedCrossRef 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 243:74–81PubMedCrossRef
4.
Zurück zum Zitat 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 23:1237–1244PubMedCrossRef 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 23:1237–1244PubMedCrossRef
5.
Zurück zum Zitat 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 63:1286–1289PubMedCrossRef 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 63:1286–1289PubMedCrossRef
6.
Zurück zum Zitat MacDonald JS (2005) Role of post-operative chemoradiation in resected gastric cancer. J Surg Oncol 90:166–170PubMedCrossRef MacDonald JS (2005) Role of post-operative chemoradiation in resected gastric cancer. J Surg Oncol 90:166–170PubMedCrossRef
7.
Zurück zum Zitat 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 63:1279–285PubMedCrossRef 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 63:1279–285PubMedCrossRef
8.
Zurück zum Zitat 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 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.
Zurück zum Zitat Chong G, Cunningham D (2005) Gastrointestinal cancer: recent developments in medical oncology. Eur J Surg Oncol 31:453–460PubMedCrossRef Chong G, Cunningham D (2005) Gastrointestinal cancer: recent developments in medical oncology. Eur J Surg Oncol 31:453–460PubMedCrossRef
10.
Zurück zum Zitat Leong T (2004) Evolving role of chemoradiation in the adjuvant treatment of gastric cancer. Expert Rev Anticancer Ther 4:585–594PubMedCrossRef Leong T (2004) Evolving role of chemoradiation in the adjuvant treatment of gastric cancer. Expert Rev Anticancer Ther 4:585–594PubMedCrossRef
11.
Zurück zum Zitat Stahl M (2004) Adjuvant chemoradiotherapy in gastric cancer and carcinoma of the oesophago-gastric junction. Onkologie 27:33–36PubMedCrossRef Stahl M (2004) Adjuvant chemoradiotherapy in gastric cancer and carcinoma of the oesophago-gastric junction. Onkologie 27:33–36PubMedCrossRef
12.
Zurück zum Zitat 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 22:2069–2077PubMedCrossRef 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 22:2069–2077PubMedCrossRef
13.
Zurück zum Zitat Hundahl SA, Wanebo HJ (2005) Changing gastric cancer treatment in the United States and the pursuit of quality. Eur J Surg Oncol 31:605–615PubMedCrossRef Hundahl SA, Wanebo HJ (2005) Changing gastric cancer treatment in the United States and the pursuit of quality. Eur J Surg Oncol 31:605–615PubMedCrossRef
14.
Zurück zum Zitat Falcone A (2003) Future strategies and adjuvant treatment of gastric cancer. Ann Oncol 14:45–47CrossRef Falcone A (2003) Future strategies and adjuvant treatment of gastric cancer. Ann Oncol 14:45–47CrossRef
15.
Zurück zum Zitat Roukos DH, Kappas AM (2005) Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol 2:98–107PubMedCrossRef Roukos DH, Kappas AM (2005) Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol 2:98–107PubMedCrossRef
16.
Zurück zum Zitat 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 24:2903–2909PubMedCrossRef 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 24:2903–2909PubMedCrossRef
17.
Zurück zum Zitat Sutter AP, Zeitz M, Scherübl H (2004) Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer. Onkologie 27:17–21PubMedCrossRef Sutter AP, Zeitz M, Scherübl H (2004) Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer. Onkologie 27:17–21PubMedCrossRef
18.
Zurück zum Zitat 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 93:241–252PubMedCrossRef 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 93:241–252PubMedCrossRef
19.
Zurück zum Zitat Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003;21:2787–2799PubMedCrossRef Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003;21:2787–2799PubMedCrossRef
20.
Zurück zum Zitat 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 10:234–241PubMedCrossRef 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 10:234–241PubMedCrossRef
21.
Zurück zum Zitat Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445–2459PubMedCrossRef Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445–2459PubMedCrossRef
22.
Zurück zum Zitat Grunwald V, Hidalgo M (2003) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95:851–867PubMedCrossRef Grunwald V, Hidalgo M (2003) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95:851–867PubMedCrossRef
23.
Zurück zum Zitat Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7:2958–2970PubMed Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7:2958–2970PubMed
24.
Zurück zum Zitat 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 13:823–835PubMedCrossRef 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 13:823–835PubMedCrossRef
25.
Zurück zum Zitat 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 162:115–132PubMed 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 162:115–132PubMed
26.
Zurück zum Zitat 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 17:579–587PubMedCrossRef 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 17:579–587PubMedCrossRef
27.
Zurück zum Zitat 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 444:324–331PubMedCrossRef 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 444:324–331PubMedCrossRef
28.
Zurück zum Zitat 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 16:641–651PubMedCrossRef 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 16:641–651PubMedCrossRef
29.
Zurück zum Zitat Hiyama T, Tanaka S, Yoshihara M, et al. (2004) Chromosomal and microsatellite instability in sporadic gastric cancer. J Gastroenterol Hepatol 19:756–760PubMedCrossRef Hiyama T, Tanaka S, Yoshihara M, et al. (2004) Chromosomal and microsatellite instability in sporadic gastric cancer. J Gastroenterol Hepatol 19:756–760PubMedCrossRef
30.
Zurück zum Zitat Kalbfleisch JD, Prentice RL (1980) The Statistical Analysis of Failure Time Data. New York, Wiley Kalbfleisch JD, Prentice RL (1980) The Statistical Analysis of Failure Time Data. New York, Wiley
31.
Zurück zum Zitat 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 44:826–837PubMed 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 44:826–837PubMed
32.
Zurück zum Zitat 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 52:182–188PubMedCrossRef 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 52:182–188PubMedCrossRef
33.
Zurück zum Zitat 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 15:455–462PubMed 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 15:455–462PubMed
Metadaten
Titel
Epidermal Growth Factor Receptor (EGFR) Expression is Associated With a Worse Prognosis in Gastric Cancer Patients Undergoing Curative Surgery
verfasst von
Gennaro Galizia
Eva Lieto
Michele Orditura
Paolo Castellano
Anna La Mura
Vincenzo Imperatore
Margherita Pinto
Anna Zamboli
Ferdinando De Vita
Francesca Ferraraccio
Publikationsdatum
01.07.2007
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 7/2007
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-007-9016-4

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