Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma

World Journal of Surgical Oncology

Ningzhi Xu²  Lvhua Wang⁵  Kelin Sun¹  Jie He¹  Xun Zhang³  Xiao Liu⁵  Wencheng Zhang⁵  Zefen Xiao⁵  Hongxia Zhu²  Qifeng Wang⁴ 

[1]Department of Thoracic Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No.17, Nanli, Panjiayuan, Beijing 100021, People’s Republic of China

[2]Laboratory of Cellular and Molecular Biology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No.17, Nanli, Panjiayuan, Beijing 100021, People’s Republic of China

[3]Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No.17, Nanli, Panjiayuan, Beijing 100021, People’s Republic of China

[4]Present working address: Department of Radiation Oncology, Sichuan Cancer Hospital, No.55, Fourth Section, Renmin South Road, Chengdu 610041, People’s Republic of China

[5]Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No.17, Nanli, Panjiayuan, Beijing 100021, People’s Republic of China

关键词: Fiducial markers;    Tumor markers;    Survival analysis;    Statistics;    Operations;    Esophageal surgery;    Esophageal cancer;   

Others  :  821152
DOI  :  10.1186/1477-7819-11-278

 received in 2013-04-17, accepted in 2013-10-06,  发布年份 2013

【 摘 要 】

Background

The overall survival of patients with esophageal squamous cell carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based on histological assessment of tumor invasion and lymph node metastasis, but a biomarker with better predictive accuracy could be more useful. Because overexpression of epidermal growth factor receptor (EGFR) has been associated with poor prognosis, this study investigated whether EGFR is an independent prognostic factor for overall survival and disease-free survival of ESCC patients.

Methods

ESCC tissue specimens from 243 patients obtained during surgical resection between 1980 and 1997 were retrieved for immunohistochemical analysis of EGFR expression.

Results

The data showed that EGFR protein was overexpressed in 187 of 243 (77%) ESCC tissues. Elevated expression was associated with higher pathologic tumor stages (P = 0.001), lymph node metastasis (P = 0.002), and higher Union for International Cancer Control (UICC) stage (P <0.0001), as well as poorer disease-free survival and overall survival of ESCC patients (P <0.0001). A multivariate analysis showed that overexpression of EGFR protein was an independent factor for disease-free survival (P = 0.003) and overall survival (P = 0.001) of these patients. Subgroup analysis of patients with stage IIA (UICC 2002) showed that EGFR overexpression was associated with poorer disease-free survival (P = 0.007) and overall survival (P = 0.010) of the patients in univariate analyses.

Conclusions

The current study demonstrated that EGFR overexpression was an independent prognostic factor for overall survival and disease-free survival of ESCC patients. However, targeting of EGFR activity using gefitinib or erlotinib could be useful for clinical treatment of ESCC patients.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Chen W, Zeng H, Zheng R, Zhang S, He J: Cancer incidence and mortality in China, 2007. Chin J Cancer Res 2012, 24:1-8.
• [2]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
• [3]Bancewicz J, Clark P, Smith D, Donnelly R, Fayers P, Weeden S, Girling D, Hutchinson T, Harvey A, Lyddiard J, Al-Jilaihawi A, Bown S, Cottier B, Jeyasingham K, Lea R, Matthews H, Moghissi K, Morritt G, Myskow M, Pagliero K, Rowland C, Yosef H, Med Res Council Oesophageal Canc: Surgical resection with or without preoperative chemotherapy in esophageal cancer: a randomised controlled trial. Lancet 2002, 359:1727-1733.
• [4]Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 1998, 339:1979-1984.
• [5]Xiao ZF, Yang ZY, Miao YJ, Wang LH, Yin WB, Gu XZ, Zhang DC, Sun KL, Chen GY, He J: Influence of number of metastatic lymph nodes on survival of curative resected thoracic esophageal cancer 7.patients and value of radiotherapy: report of 549 cases. Int J Radiat Oncol Biol Phys 2005, 62:82-90.
• [6]Kawahara K, Maekawa T, Okabayashi K, Shiraishi T, Yoshinaga Y, Yoneda S, Hideshima T, Shirakusa T: The number of lymph node metastases influences survival in esophageal cancer. J Surg Oncol 1998, 67:160-163.
• [7]Rice TW, Rusch VW, Apperson-Hansen C, Allen MS, Chen LQ, Hunter JG, Kesler KA, Law S, Lerut TE, Reed CE, Salo JA, Scott WJ, Swisher SG, Watson TJ, Blackstone EH: Worldwide esophageal cancer collaboration. Dis Esophagus 2009, 22:1-8.
• [8]Sobin LCW, Wittekind C, International Union Against Cancer (UICC): TNM Classification of Malignant Tumours. 6th edition. New York: John Wiley and Sons; 2002.
• [9]Sobin LH, Gospodarowicz MK, Wittekind C, International Union Against Cancer (UICC): TNM Classification of Malignant Tumours. 7th edition. New York: Wiley-Liss; 2010.
• [10]Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, Seetharam S, Koons A, Hari DM, Kufe DW, Weichselbaum RR: Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 1999, 59:3374-3378.
• [11]Kanamori A, Abe Y, Yajima Y, Manabe Y, Ito K: Epidermal growth factor receptors in plasma membranes of normal and diseased human thyroid glands. J Clin Endocrinol Metab 1989, 68:899-903.
• [12]Hoos A, Urist MJ, Stojadinovic A, Mastorides S, Dudas ME, Leung DH, Kuo D, Brennan MF, Lewis JJ, Cordon-Cardo C: Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors. Am J Pathol 2001, 158:1245-1251.
• [13]Mayer A, Takimoto M, Fritz E, Schellander G, Kofler K, Ludwig H: The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer 1993, 71:2454-2460.
• [14]Nicholson RI, Gee JM, Harper ME: EGFR and cancer prognosis. Eur J Cancer 2001, 37(Suppl 4):S9-S15.
• [15]Perez EA: The role of adjuvant monoclonal antibody therapy for breast cancer: rationale and new studies. Curr Oncol Rep 2001, 3:516-522.
• [16]Gibault L, Metges JP, Conan-Charlet V, Lozac’h P, Robaszkiewicz M, Bessaguet C, Lagarde N, Volant A: Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer 2005, 93:107-115.
• [17]Yano H, Shiozaki H, Kobayashi K, Yano T, Tahara H, Tamura S, Mori T: Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma. Cancer 1991, 67:91-98.
• [18]Siegel R, Ahmedin Jemal D: Cancer Facts & Figures. Atlanta: American Cancer Society, Inc.; 2013.
• [19]Hanawa M, Suzuki S, Dobashi Y, Yamane T, Kono K, Enomoto N, Ooi A: EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer 2006, 118:1173-1180.
• [20]Miyawaki M, Hijiya N, Tsukamoto Y, Nakada C, Kawahara K, Moriyama M: Enhanced phosphorylation of the epidermal growth factor receptor at the site of tyrosine 992 in esophageal carcinomas. APMIS 2008, 116:1097-1106.
• [21]Boone J, van Hillegersberg R, Offerhaus GJ, van Diest PJ, Borel Rinkes IH, Ten Kate FJ: Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis. Dis Esophagus 2009, 22:496-504.
• [22]Wang KL, Wu TT, Choi IS, Wang H, Resetkova E, Correa AM, Hofstetter WL, Swisher SG, Ajani JA, Rashid A, Albarracin CT: Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Cancer 2007, 109:658-667.
• [23]Wilkinson NW, Black JD, Roukhadze E, Driscoll D, Smiley S, Hoshi H, Geradts J, Javle M, Brattain M: Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma. J Gastrointest Surg 2004, 8:448-453.
• [24]Hoshino M, Fukui H, Ono Y, Sekikawa A, Ichikawa K, Tomita S, Imai Y, Imura J, Hiraishi H, Fujimori T: Nuclear expression of phosphorylated EGFR is associated with poor prognosis of patients with esophageal squamous cell carcinoma. Pathobiology 2007, 74:15-21.
• [25]Gotoh M, Takiuchi H, Kawabe S, Ohta S, Kii T, Kuwakado S, Katsu K: Epidermal growth factor receptor is a possible predictor of sensitivity to chemoradiotherapy in the primary lesion of esophageal squamous cell carcinoma. Jpn J Clin Oncol 2007, 37:652-657.
• [26]Kii T, Takiuchi H, Kawabe S, Gotoh M, Ohta S, Tanaka T, Kuwakado S, Nishitani H, Katsu K: Evaluation of prognostic factors of esophageal squamous cell carcinoma (stage II-III) after concurrent chemoradiotherapy using biopsy specimens. Jpn J Clin Oncol 2007, 37:583-589.
• [27]Oda K, Matsuoka Y, Funahashi A, Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005, 1:2005 0010.
• [28]Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304:1497-1500.