The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas

Background The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. Materials and methods Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. Results Membranous c-erbB-2 levels ranged widely in the studied tumors (44–112,000 NHU/mg protein). Median c-erbB-2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p=0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p=0.01 and p=0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. Conclusion Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.

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Epidermal Growth Factor Receptor and c-erbB-2 Contents in Unresectable (UICC R1 or R2) Gastric Cancer

The International Journal of Biological Markers ◽

10.1177/172460080301800308 ◽

2003 ◽

Vol 18 (3) ◽

pp. 200-206 ◽

Cited By ~ 7

Author(s):

I. García ◽

J.M. Del Casar ◽

M.D. Corte ◽

M.T. Allende ◽

J.L. García-Muñiz ◽

...

Keyword(s):

Gastric Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Radioligand Binding ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Membrane Receptors ◽

Gastric Carcinomas ◽

Epidermal Growth

Background Epidermal growth factor receptor (EGFR) and c-erbB-2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis. The objective of this work was to evaluate the EGFR and c-erbB-2 levels in non-resectable gastric carcinomas, their possible relationship with a variety of clinicopathological tumor parameters, and their prognostic significance. Methods This was a prospective analysis of 65 patients with unresectable gastric carcinomas (UICC R1 or R2), who underwent palliative surgery and were followed up for a median period of 13 months. Membranous EGFR levels were examined by radioligand binding assays and cytosolic c-erbB-2 levels by means of an immunoenzymatic assay. Results There was a wide variability in EGFR (80.3-2910 fmol/mg of protein) and c-erbB-2 (0.4-10071 NHU/mg of protein) levels in neoplastic tissues from patients with unresectable gastric carcinomas. Median c-erbB2 was significantly higher in tumors of the intestinal type than in tumors of the diffuse type (p=0.035) and in R2 than in R1 tumors (p=0.016). Statistical analysis showed that there was no relationship between tumor c-erbB-2 or EGFR content and any other patient or tumor characteristics. However, high levels of EGFR were significantly associated with a shorter overall survival (p=0.01). Conclusion Our data suggest a role of both transmembrane proteins in the progression of gastric cancer. EGFR and c-erbB-2 contents in unresectable gastric cancer could be utilized as appropriate biological markers for selecting candidates for treatment based on EGFR and/or c-erbB-2 inhibition.

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