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
. 2014 Jan;17(1):76-86.
doi: 10.1007/s10120-013-0236-z. Epub 2013 Feb 28.

Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors

Alexandre Andrade Anjos Jácome  1 , Durval R Wohnrath, Cristovam Scapulatempo Neto, Estela C Carneseca, Sérgio V Serrano, Luciano Souza Viana, João S Nunes, Edson Z Martinez, José Sebastião Santos
Affiliations

Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors

Alexandre Andrade Anjos Jácome et al. Gastric Cancer. 2014 Jan.

Abstract

Background: There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer.

Methods: This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution.

Results: Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence.

Conclusions: According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Kaplan–Meier overall survival curve
Fig. 2
Fig. 2
Survival curves estimated by Kaplan–Meier method and parametric models assuming Weibull (a), exponential (b) and Weibull mixture model incorporating long-term survivors (c) distributions
Fig. 3
Fig. 3
Graphic representation of survival functions estimated by the Kaplan–Meier method versus survival functions estimated by the parametric models assuming Weibull (a), exponential (b), and Weibull mixture model incorporating long-term survivors (c) distributions
Fig. 4
Fig. 4
Examples of positive immunohistochemistry for HER1 staining in the cytoplasm (a), for HER1 in the membrane (b), for HER2 in the membrane (c), for HER3 in the cytoplasm (d), for HER4 in the cytoplasm (e), and for HER4 in the membrane (f). Magnification: a–f ×400
Fig. 5
Fig. 5
Instantaneous risk of death
Fig. 6
Fig. 6
Estimation of parameters of the regression model incorporating long-term survivors with Weibull distribution and related covariates
See this image and copyright information in PMC

References

    1. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(suppl 4):S9–S15. doi: 10.1016/S0959-8049(01)00231-3. - DOI - PubMed
    1. Sithanandam G, Anderson LM. The ERBB3 receptor in cancer and cancer gene therapy. Cancer Gene Ther. 2008;15(7):413–448. doi: 10.1038/cgt.2008.15. - DOI - PMC - PubMed
    1. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19(3):183–232. doi: 10.1016/1040-8428(94)00144-I. - DOI - PubMed
    1. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19(9):1523–1529. doi: 10.1093/annonc/mdn169. - DOI - PubMed
    1. Hudis CA. Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51. doi: 10.1056/NEJMra043186. - DOI - PubMed

Publication types