Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb 10;100(3):487-93.
doi: 10.1038/sj.bjc.6604885. Epub 2009 Jan 20.

Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients

J D Barros-Silva  1 , D Leitão, L Afonso, J Vieira, M Dinis-Ribeiro, M Fragoso, M J Bento, L Santos, P Ferreira, S Rêgo, C Brandão, F Carneiro, C Lopes, F Schmitt, M R Teixeira
Affiliations

Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients

J D Barros-Silva et al. Br J Cancer. .

Abstract

The clinical significance of ERBB2 amplification/overexpression in gastric cancer remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric carcinomas using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and compared the findings with histopathological characteristics and with disease-specific survival. ERBB2 overexpression (2+ and 3+) and amplification (ratio ERBB2/CEP17 >or= 2) were found in 43 (9.3%) and 38 (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases scored as 3+ (all positive by FISH). One out of six carcinomas scored as 1+ and 12 out of 18 carcinomas scored as 2+ were positive by FISH. ERBB2 amplification was associated with gastric carcinomas of intestinal type (P=0.007) and with an expansive growth pattern (P=0.021). ERBB2 amplification was detected in both histological components of two mixed carcinomas, indicating a common clonal origin. A statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P=0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients, and that further studies are warranted to evaluate whether patients whose gastric carcinomas present ERBB2 amplification/overexpression may benefit from therapy targeting this surface receptor.

PubMed Disclaimer

Figures

Figure 1
Figure 1
ERBB2 protein expression evaluated by IHC in gastric carcinomas. (A) Negative ERBB2 expression (0) (original magnification × 400); (B) ERBB2 positive expression –(3+) (original magnification × 400); (C) mixed type carcinoma with ERBB2 overexpression in both histological components (original magnification × 100).
Figure 2
Figure 2
Fluorescence in situ hybridisation targeting ERBB2 in gastric carcinoma specimens (original magnification, × 1000). Red labelled probes target the ERBB2, green labelled probes target chromosome 17 centromere, and nuclei (blue) are stained with DAPI. (A) intestinal type carcinoma (score 0 by IHC) with no ERBB2 amplification; (B) intestinal type carcinoma (score 2+ by IHC) showing ERBB2 amplification; (C) intestinal type carcinoma (score 1+ by IHC) showing ERBB2 amplification. A full colour version of this figure is available at the British Journal of Cancer online.
Figure 3
Figure 3
Survival curves of gastric cancer patients, (A) Kaplan–Meier plot for disease-specific survival of 256 gastric cancer patients according to ERBB2 amplification status. (B) Kaplan–Meier plot for disease-specific survival of 75 expansive-type gastric cancer patients according to ERBB2 amplification status.
See this image and copyright information in PMC

References

    1. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T (1986) The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232: 1644–1646 - PubMed
    1. Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Hofler H (1994) E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 54: 3845–3852 - PubMed
    1. Carneiro F (1997) Classification of gastric carcinomas. Curr Diag Pathol 4: 51–59
    1. Carvalho B, Buffart TE, Reis RM, Mons T, Moutinho C, Silva P, van Grieken NC, Grabsch H, Van de Velde CJ, Ylstra B, Meijer GA, Carneiro F (2006) Mixed gastric carcinomas show similar chromosomal aberrations in both their diffuse and glandular components. Cell Oncol 28: 283–294 - PMC - PubMed
    1. Cimerman M, Repse S, Jelenc F, Omejc M, Bitenc M, Lamovec J (1994) Comparison of Lauren's, Ming's and WHO histological classifications of gastric cancer as a prognostic factor for operated patients. Int Surg 79: 27–32 - PubMed

Publication types