The online version of this article (doi:10.1186/1477-7819-10-14) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
WWP designed partial molecular experiments, and drafted the manuscript. WKN and GQ performed partial molecular experiments and revised the manuscript. CLQ participated in the overall design, study coordination and finalized the draft of the manuscript. All authors read and approved the final manuscript.
The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.
From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.
In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.
Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.
Authors’ original file for figure 112957_2011_932_MOESM1_ESM.jpeg
Mendelsohn J: Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol. 2002, 20 (18 suppl): 1S-13S. PubMed
Cohen MH, Williams GA, Sridhara R, Chen G, McGuinn WD, Morse D, Abraham S, Rahman A, Liang C, Lostritto R, Baird A, Pazdur R: United States Food and Drug Administration drug approval summary: gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res. 2004, 10 (4): 1212-8. 10.1158/1078-0432.CCR-03-0564. CrossRefPubMed
Kris MG, Natale RB, Herbst RS, Lynch TJ, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC: Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003, 290 (16): 2149-58. 10.1001/jama.290.16.2149. CrossRefPubMed
Paez JG, Jänne 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 (5676): 1497-500. 10.1126/science.1099314. CrossRefPubMed
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004, 350 (21): 2129-39. 10.1056/NEJMoa040938. CrossRefPubMed
Dobelbower MC, Russo SM, Raisch KP, Seay LL, Clemons LK, Suter S, Posey J, Bonner JA: Epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, and concurrent 5-fluorouracil, cisplatin and radiotherapy for patients with esophageal cancer: a phase I study. Anticancer Drugs. 2006, 17 (1): 95-102. 10.1097/01.cad.0000185178.26862.4c. CrossRefPubMed
Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, Meijer GA, Vervenne WL, Richel DJ, Van Groeningen C, Giaccone G: Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol. 2006, 24 (10): 1612-9. 10.1200/JCO.2005.03.4900. CrossRefPubMed
He YT, Hou J, Chen ZF, Qiao CY, Song GH, Meng FS, Ji HX, Chen C: Analysis on epidemiology of gastric cardia carcinoma in high incidence area of esophageal carcinoma. Chin J Pub Heal. 2006, 22 (12): 1434-35.
Chen WQ, Zhang SW, Chen ZF: An epidemiologic trend analysis on cardiac cancer in high incidence areas of esophageal cancer and gastric cancer in China. Bulletin Chin Cancer. 2008, 17 (12): 998-1000.
Shao LF, Gao ZR, Wei GQ, Xu JL, Chen MY, Cheng JH: Surgical treatment of carcinoma of the esophagus and gastric cardia: 34-year investigation. Chin J Surgery. 2001, 39 (1): 44-6.
Huang YS, Yang JJ, Zhang XC, Yang XN, Huang YJ, Xu CR, Zhou Q, Wang Z, Su J, Wu YL: Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer. Chin Med J (Engl). 2011, 124 (16): 2457-60.
D'Angelo SP, Pietanza MC, Johnson ML, Riely GJ, Miller VA, Sima CS, Zakowski MF, Rusch VW, Ladanyi M, Kris MG: Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol. 2011, 29 (15): 2066-70. 10.1200/JCO.2010.32.6181. PubMedCentralCrossRefPubMed
Choi JE, Park SH, Kim KM, Lee WK, Kam S, Cha SI, Kim CH, Kang YM, Kim YC, Han SB, Jung TH, Park JY: Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: a case-control study. BMC Cancer. 2007, 7: 198-206. 10.1186/1471-2407-7-198. CrossRef
Kaneko K, Kumekawa Y, Makino R, Nozawa H, Hirayama Y, Kogo M, Konishi K, Katagiri A, Kubota Y, Muramoto T, Kushima M, Ohmori T, Oyama T, Kagawa N, Ohtsu A, Imawari M: EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. Front Biosci. 2010, 15: 65-72. 10.2741/3607. CrossRef
- Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction
- BioMed Central
Neu im Fachgebiet Chirurgie
e.Med Kampagnen-Visual, Mail Icon II