Onkologie. 2010:4(2):115-119

HER-2/neu testing in gastric carcinoma - new challenge and hope?

Aleš Ryška, Tomáš Rozkoš, Jan Laco
Fingerlandův ústav patologie LF UK a FN, Hradec Králové

Gastric carcinoma is the second cause of cancer related death worldwide. Prognosis significantly varies among patients within the same

stage, therefore oncologists urge for identification of new prognostic and predictive markers, such as HER-2/neu (HER2). Stimulation

of HER2 triggers molecular pathway resulting in increased proliferation, blocked apoptosis, loss of differentiation and increased tumor

invasion. HER2 is a negative prognostic factor, associated with increased invasiveness, serosal involvement, lymph-node metastases

and shorter survival, as well as a negative predictive marker and target for trastuzumab treatment.

There are two methods of HER2 detection – immunohistochemistry (IHC) and in situ hybridisation (ISH). Positivity of HER2 in gastric

cancer ranges from 6,8 to 34 % (mean 17,6 %) in IHC detection, and 7,1–42,6 % (mean 19,2 %) in ISH detection, respectively. HER2 is more

often positive in intestinal than in diffuse type.

HER2 detection in gastric carcinoma shows certain specific features – positive cells show either complete or incomplete basolateral (Ushaped)

membranous expression. Due to more frequent inhomogenity of tumor population, the threshold has been set at 10 % of positive

cells in resection specimens, but even one cohesive cluster of positive (2+ or 3+) neoplastic cells is sufficient in biopsy samples.

Keywords: gastric carcinoma, HER-2/neu, c-erbB-2, immunohistochemistry, in situ hybridization

Published: May 1, 2010  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ryška A, Rozkoš T, Laco J. HER-2/neu testing in gastric carcinoma - new challenge and hope? Onkologie. 2010;4(2):115-119.
Download citation

References

  1. Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. 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: 2201-2209. Go to original source... Go to PubMed...
  2. Barros-Silva JD, Leitao D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer 2009; 100: 487-493. Go to original source... Go to PubMed...
  3. Fukushige S, Matsubara K, Yoshida M, Sasaki M, Suzuki T, Semba K, et al. Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 1986; 6: 955-958. Go to original source... Go to PubMed...
  4. Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008; 52: 797-805. Go to original source... Go to PubMed...
  5. Im SA, Lee KE, Nam E, Kim DY, Lee JH, Han HS, et al. Potential prognostic significance of p185 (HER2) overexpression with loss of PTEN expression in gastric carcinomas. Tumori 2005; 91: 513-521. Go to original source... Go to PubMed...
  6. Kim MA, Jung EJ, Lee HS, Lee HE, Jeon YK, Yang HK, et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol 2007; 38: 1386-1393. Go to original source... Go to PubMed...
  7. Kim SY, Kim HP, Kim YJ, Oh do Y, Im SA, Lee D, et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int J Oncol 2008; 32: 89-95. Go to original source...
  8. Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol 2003; 33: 173-179. Go to original source... Go to PubMed...
  9. Lund MJ, Butler EN, Hair BY, Ward KC, Andrews JH, OpreaIlies G, et al. Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: a population-based study and first report. Cancer 2010. Go to original source...
  10. Marla S, Cardale J, Dodwell DJ, Skene AI, Abram P, Palmieri C, et al. A multi centre audit of HER2 positive Early Breast Cancers and the reasons why patients do not receive Trastuzumab therapy. Eur J Cancer Suppl. 2010; 8: 85 Abstract 94. Go to original source...
  11. Matsui Y, Inomata M, Tojigamori M, Sonoda K, Shiraishi N, Kitano S. 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: 681-685.
  12. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006; 51: 1371-1379. Go to original source... Go to PubMed...
  13. Rebischung C, Barnoud R, Stefani L, Faucheron JL, Mousseau M. The effectiveness of trastuzumab (Herceptin) combined with chemotherapy for gastric carcinoma with overexpression of the c-erbB-2 protein. Gastric Cancer 2005; 8: 249-252. Go to original source... Go to PubMed...
  14. Risio M, De Rosa G, Sarotto I, Casorzo L, Capussotti L, Torchio B, et al. HER2 testing in gastric cancer: molecular morphology and storage time-related changes in archival samples. Int J Oncol 2003; 23: 1381-1387. Go to original source...
  15. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest 2001; 19: 554-568. Go to original source... Go to PubMed...
  16. Shinohara H, Morita S, Kawai M, Miyamoto A, Sonoda T, Pastan I, et al. Expression of HER2 in human gastric cancer cells directly correlates with antitumor activity of a recombinant disulfide-stabilized anti-HER2 immunotoxin. J Surg Res 2002; 102: 169-177. Go to original source... Go to PubMed...
  17. Shun CT, Wu MS, Lin JT, Wang HP, Houng RL, Lee WJ, et al. An immunohistochemical study of E-cadherin expression with correlations to clinicopathological features in gastric cancer. Hepatogastroenterology 1998; 45: 944-949. Go to PubMed...
  18. Takehana T, Kunitomo K, Kono K, Kitahara F, Iizuka H, Matsumoto Y, et al. Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. Int J Cancer 2002; 98: 833-837. Go to original source... Go to PubMed...
  19. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, 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: 273-278. Go to original source... Go to PubMed...
  20. Van Cutsem E, Kang Y, Shen L, Lordick F, Ohtsu A, Satoh T, et al. Trastuzumab added to standard chemotherapy (CT) as first-line treatment in human epidermal growth factor receptor 2 (HER-2)-positive advanced gastric cancer (GC): efficacy and safety results from the Phase III ToGA trial. Eur J Cancer Suppl 2009; 7: 7(Abstract 7BA). Go to original source...
  21. Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, 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: 65-71. Go to original source... Go to PubMed...
  22. Yonemura Y, Ninomiya I, Ohoyama S, Fushida S, Kimura H, Tsugawa K, et al. Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer. Oncology 1992; 49: 363-367. Go to original source... Go to PubMed...
  23. Yonemura Y, Ninomiya I, Ohoyama S, Kimura H, Yamaguchi A, Fushida S, et al. Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma. Cancer 1991; 67: 2914-2918. Go to original source...
  24. Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res 1991; 51: 1034-1038.




Oncology

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.