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Predictive diagnosis of HER2 in gastric adenocarcinoma


Authors: Daum O.ihash2ihash4ihash6 1 2 3 3
Authors‘ workplace: Šiklův ústav patologie LF UK v Plzni a FN Plzeň, Bioptická laboratoř, s. r. o., Plzeň, Fingerlandův ústav patologie LF UK a FN, Hradec Králové 1
Published in: Čes.-slov. Patol., 47, 2011, No. 4, p. 160-163
Category: Reviews Article

Overview

Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). This receptor is overexpressed in approximately 20% of gastric adenocarcinomas. The overexpression is associated with a worse prognosis, but on the other hand, patients with HER2-positive cancers were shown to benefit from the addition of trastuzumab to standard chemotherapy. To begin the targeted therapy with trastuzumab, HER2 testing is now mandatory with immunohistochemistry being the primary test followed by in situ hybridization analysis of HER2 amplification in cases with equivocal immunopositivity (score 2+). The immunohistochemical HER2 scoring system has been modified to include incomplete basolateral and lateral membrane staining, and to differentiate between surgical and endoscopical samples of the tumor. Benefit from trastuzumab treatment can be expected in tumors showing an immunohistochemical score 3+, and in cases with score 2+ and a positive finding of HER2 amplification. Clinical trials with further monoclonal antibodies and receptor tyrosine kinase inhibitors are recently ongoing to broaden the spectrum of possibilities of a multitargeted approach to the treatment of gastric cancer.

Keywords:
carcinoma – HER2 – stomach – targeted therapy – trastuzumab


Sources

1. Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007; 18(3): 581–592.

2. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24(14): 2137–2150.

3. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344(11): 783–792.

4. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376(9742): 687–697.

5. Schechter AL, Hung MC, Vaidyanathan L, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985; 229(4717): 976–978.

6. Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230(4730): 1132–1139.

7. Carraway KL, 3rd, Sliwkowski MX, Akita R, et al. The erbB3 gene product is a receptor for heregulin. J Biol Chem 1994; 269(19): 14303–14306.

8. Worthylake R, Opresko LK, Wiley HS. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 1999; 274(13): 8865–8874.

9. Olayioye MA, Graus-Porta D, Beerli RR, et al. ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner. Mol Cell Biol 1998; 18(9): 5042–5051.

10. Sepp-Lorenzino L, Eberhard I, Ma Z, et al. Signal transduction pathways induced by heregulin in MDA-MB-453 breast cancer cells. Oncogene 1996; 12(8): 1679–1687.

11. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008; 52(7): 797–805.

12. Park DI, Yun JW, Park JH, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006; 51(8): 1371–1379.

13. Yano T, Doi T, Ohtsu A, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 2006; 15(1): 65–71.

14. Zhang XL, Yang YS, Xu DP, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 2009; 33(10): 2112–2118.

15. Uchino S, Tsuda H, Maruyama K, et al. Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer 1993; 72(11): 3179–3184.

16. Nakajima M, Sawada H, Yamada Y, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 1999; 85(9): 1894–1902.

17. Allgayer H, Babic R, Gruetzner KU, et al. c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol 2000; 18(11): 2201–2209.

18. Matsui Y, Inomata M, Tojigamori M, et al. Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model. Int J Oncol 2005; 27(3): 681–685.

19. Tanner M, Hollmen M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005; 16(2): 273–278.

20. Ruschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010; 457(3): 299–307.

21. Kimura M, Tsuda H, Morita D, et al. A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based on correlation of fluorescence in situ hybridization and immunohistochemical measurements. Virchows Arch 2004; 445(3): 255–262.

22. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/ College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007; 131(1): 18–43.

23. Kim JG, Chung HY, Yu W. Recent advances in chemotherapy for advanced gastric cancer. World J Gastrointest Oncol 2010; 2(7): 287–294.

24. Okines AF, Cunningham D. Trastuzumab in gastric cancer. Eur J Cancer 2010; 46(11): 1949–1959.

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