World J Surg (2008) 32:1225–1226 DOI 10.1007/s00268-007-9434-3
EGFR as a Prognostic Marker for Gastric Cancer Theodore Liakakos Æ Nikolaos Xeropotamos Æ Dimosthenis Ziogas Æ Dimitrios Roukos
Published online: 28 January 2008 Ó Socie´te´ Internationale de Chirurgie 2008
To the Editor Current treatment decisions on gastric cancer are based on the TNM staging system. But because of well-recognized limitations [1], there is urgent need for prognostic biomarkers and novel targeted therapy. Overall, prognosis of gastric cancer is poor, with a 5-year survival rate in the USA of only 23% [2]. At present, cure can practically be achieved primarily in localized disease when appropriate local treatment, as adequate D2 surgery, is applied [3–6]. Most patients with stages I and II gastric adenocarcinona [7] or lymphoma [8] have local disease and can be cured with adequate D2 surgery [9, 10] or, alternatively, limited D1 surgery plus chemoradiation [11, 12]. The addition of systematic adjuvant chemotheraphy can increase the 5– year survival rate but only moderately, by 13% [13]. All these data suggest the need for prognostic and predictive biomarkers to identify the patients who would most benefit from systemic adjuvant treatment [14]. Therefore, the report by Galizia et al. [15] in the July issue of the World Journal of Surgery on the potential use of EGFR as a prognostic tool is very useful. EGFR could potentially be used for making decisions about adjuvant chemotherapy and/or anti-EGFR targeted therapy for gastric cancer. This is an excellent but very complex topic. In the era of network biology [16], high-throughput technologies now enable the identification of new genes, mutations, and multiple oncogenic pathways, which are involved in various cancers including gastric cancer [17]. It is likely therefore, that in gastric carcinogenesis, progression, and metastasis, several other signaling pathways are T. Liakakos N. Xeropotamos D. Ziogas D. Roukos (&) Department of Surgery, Ioannina University School of Medicine, 451 10 Ioannina, Greece e-mail:
[email protected]
activated beyond EGFR [18]. This aspect is also supported by the lack of association between EGFR expression levels and anti-EGFR agents for gastric cancer and other solid tumors [19]. Molecular and genetic tools hold great promise for personalized cancer treatment [18, 20–22]. For example, genetic testing has already been incorporated into the prevention and treatment of hereditary diffuse gastric cancer and hereditary breast ovarian cancer syndromes [23–28]. However, much more basic and clinical research work is needed to reach clinical treatment decisions for tailoring the best combinatorial treatment for individual patients with gastric cancer [29]. References 1. Roukos DH, Kappas AM (2005) Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol 2:98–107 2. Jemal A, Siegel R, Ward E et al. (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66 3. Roukos DH (1998) Extended lymphadenectomy in gastric cancer: when, for whom and why. Ann R Coll Surg Engl 80:16–24 4. Siewert JR, Bottcher K, Stein HJ et al. (1998) Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 228:449–461 5. Roukos DH, Kappas AM (2002) Targeting the optimal extent of lymph node dissection for gastric cancer. J Surg Oncol 81:59–62 6. Sano T (2007) Tailoring treatments for curable gastric cancer. Br J Surg 94:263–264 7. Roukos DH (2004) Early-stage gastric cancer: a highly treatable disease. Ann Surg Oncol 11:127–129 8. Roukos DH, Hottenrott C, Encke A et al. (1994) Primary gastric lymphomas: a clinicopathologic study with literature review. Surg Oncol 3:115–125 9. Kappas AM, Fatouros M, Roukos DH (2004) Is it time to change surgical strategy for gastric cancer in the United States? Ann Surg Oncol 11:727–730 10. Roukos DH (2000) Extended (D2) lymph node dissection for gastric cancer: do patients benefit? Ann Surg Oncol 7:253–255
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1226 11. Macdonald JS, Smalley SR, Benedetti J et al. (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730 12. Roukos DH (2002) Adjuvant chemoradiotherapy in gastric cancer: wave goodbye to extensive surgery? Ann Surg Oncol 9:220–221 13. Cunningham D, Allum WH, Stenning SP et al. (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20 14. Briasoulis E, Fatouros M, Roukos DH (2007) Level I evidence in support of perioperative chemotherapy for operable gastric cancer: sufficient for wide clinical use? Ann Surg Oncol 14:2691–2695 15. Galizia G, Lieto E, Orditura M et al. (2007) 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 16. Friedman A, Perrimon N (2007) Genetic screening for signal transduction in the era of network biology. Cell 128:225–231 17. Greenman C, Stephens P, Smith R et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446:153–158 18. Roukos DH, Murray S, Briasoulis E (2007) Molecular genetic tools shape a roadmap towards a more accurate prognostic prediction and personalized management of cancer. Cancer Biol Ther 6:308–312 19. Valverde CM, Macarulla T, Casado E et al. (2006) Novel targets in gastric and esophageal cancer. Crit Rev Oncol Hematol 59:128–138 20. Roukos DH (2008) Innovative genomic-based model for personalized treatment of gastric cancer: integrating current standards and new technologies. Expert Rev Mol Diagn 8(1):29–39
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World J Surg (2008) 32:1225–1226 21. Roukos DH (2008) HER2 and response to paclitaxel in nodepositive breast cancer. N Engl J Med 358:197, authors reply 198 22. Briasoulis E, Liakakos T, Dova L et al. (2006) Selecting a specific pre- or postoperative adjuvant therapy for individual patients with operable gastric cancer. Expert Rev Anticancer Ther 6:931–939 23. Roukos DH, Kappas AM, Tsianos E (2002) Role of surgery in the prophylaxis of hereditary cancer syndromes. Ann Surg Oncol 9:607–609 24. Roukos DH, Agnanti NJ, Paraskevaidis E et al. (2002) Approaching the dilemma between prophylactic bilateral mastectomy or oophorectomy for breast and ovarian cancer prevention in carriers of BRCA1 or BRCA2 mutations. Ann Surg Oncol 9:941–943 25. Agnantis NJ, Paraskevaidis E, Roukos D (2004) Preventing breast, ovarian cancer in BRCA carriers: rationale of prophylactic surgery and promises of surveillance. Ann Surg Oncol 11: 1030–1034 26. Fatouros M, Baltoyiannis G, Roukos DH (2007) The predominant role of surgery in the prevention and new trends in the surgical treatment of hereditary breast ovarian cancer. Ann Surg Oncol doi:10.1245/s10434-007-9612-4, [Epub ahead of print] 27. Roukos DH, Briasoulis E (2007) Individualized preventive and therapeutic management of hereditary breast ovarian cancer. Nat Clin Pract Oncol 4:578–590 28. Roukos DH (2007) Prognosis of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357(15):1555– 1556; author reply 1556 29. Liakakos T, Roukos DH (in press) More controversy than ever – Challenges and promises towards personalized treatment of gastric cancer. Ann Surg Oncol doi:10.1245/s10434-007-9798-5
