The objective of this work was to evaluate the epidermal growth factor receptor (EGFR) content in gastric cancer, its possible relationship with clinicopathological parameters of tumors and its prognostic significance. Membranous EGFR levels were examined by radioligand binding assays in 110 patients with gastric cancer. The mean follow-up period was 30.7 months. EGFR levels of tumors ranged widely, from 0.3 to 510 fmol/mg protein. EGFR levels were significantly higher (p<0.0005) in neoplastic tissue than in paired adjacent mucosa samples (median) (n= 84; 8.7 vs. 3.9 fmol/mg protein). Intratumoral EGFR levels were significantly correlated with tumor stage (p<0.05), and were higher in patients with stage III tumors (median) (7.6, 6.4, 12.3 and 7.5 fmol/mg protein for stages I, II, III and IV, respectively). In addition, the tumor/mucosa ratios of the EGFR content were significantly higher (p<0.05) in patients with stage III tumors (1, 1.8, 3.9, and 0.92, respectively). Although there was no significant relationship between EGFR levels of tumors and overall survival, the results suggest a role for EGFR in tumor progression of gastric cancer.
DownwardJ., ParkerP., WaterfieldM.D.Autophosphorylation sites on the epidermal growth factor receptor.Nature1984; 311: 483–5.
2.
BarnardJ.A., BeauchampR.D., RusselW.E., DuboisR.N., CoffeyR.J.Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology.Gastroenterology1995; 108: 564–80.
3.
WoodburnJ.R.The epidermal growth factor receptor and its inhibition in cancer therapy.Pharmacol Ther1999; 82: 241–50.
4.
SalomonD.S., BrandtR., CiardelloF., NormannoN.Epidermal growth factor-related peptides and their receptors in human malignancies.Crit Rev Oncol Hematol1995; 19: 183–232.
5.
SakaiK., MoriS., KawamotoT.Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas.J Natl Cancer Inst1986; 77: 1047–52.
6.
YasuiW., SumiyoshiH., HataJ.Expression of epidermal growth factor receptor in human gastric and colonic carcinomas.Cancer Res1988; 48: 137–41.
7.
YonemuraY., SugiyamaK., FujimuraT.Epidermal growth factor receptor status and S-phase fractions in gastric carcinoma.Oncology1989; 46: 158–61.
8.
IidaA., HiroseK., AraiM., YamaguchiA., NakagawaraG.Relationships among the expression of epidermal growth factor, proliferating cell nuclear antigen labeling index, and lymph node metastasis in gastric cancer.Oncology1995; 52: 189–95.
9.
Sanz-OrtegaJ., SteinbergS.M., MoroE.Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-erbB2, c-myc and EGFr as prognostic factors in gastric cancer.Histol Histopathol2000; 15: 455–62.
PeláezM.C., RuibalA., AzaJ.Adenocarcinoma gástrico: expresión de la oncoproteína neu/c-erbB-2, receptor del factor de crecimiento epidérmico, catepsina D, receptor de progesterona y glucoproteína asociada a tumores-72 en función del tipo histológico.Rev Esp Enferm Dig1999; 91: 826–31.
12.
BennetC., PatersonI.M., CorbishleyC.M., LuqmaniY.A.Expression of growth factor and epidermal growth factor receptor encoded transcripts in human gastric tissues.Cancer Res1989; 49: 2104–11.
13.
YoshidaK., TsudaT., MatsumuraT.Amplification of epidermal growth factor receptor (EGFR) gene and onco-genes in human gastric carcinomas.Virchow Archiv B Cell Pathol1989; 57: 285–90.
14.
HouldsworthJ., Cordon-CardoC., LadanyiM., KelsenD.P., ChagantiR.S.K.Gene amplification in gastric and esophageal adenocarcinomas.Cancer Res1990; 50: 6417–22.
15.
HironoY., TsugawaK., FushidaS.Amplification of epidermal growth factor receptor gene and its relationship to survival in human gastric cancer.Oncology1995; 52: 182–8.
16.
AnzaiH.Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence.Eur J Cancer1998; 34: 558–65.
LaurenP.The two histological main types of gastric carcinoma: diffuse and so-called intestinal type carcinomas. An attempt at a histological classification.Acta Pathol Microbiol Scand1965; 64: 31–49.
20.
BradfordM.M.A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem1976; 72: 248–54.
21.
MarchalonisJ.J.An enzymatic method for the trace iodination of immunoglobulins and other proteins.Biochem J1969; 13: 299–305.
22.
FormentoJ.L., FrancoualM., FormentoP.Epidermal growth factor receptor assay: validation of a single point method and application to breast cancer.Breast Cancer Res Treat1990; 17: 211–9.
23.
CappellettiV., BrivioM., MiodiniP., GranataG., CoradiniD., Di FronzoG.Simultaneous estimation of epidermal growth factor receptors and steroid receptors in a series of 136 resectable primary breast tumors.Tumor Biol1988; 9: 200–11.
24.
KaplanE.L., MeierP.Nonparametric estimation from incomplete observations.J Am Stat Assoc1958; 53: 457–81.
25.
MantelN., MyersM.Problems of convergence of maximum likehood iterative procedures in multiparameter situations.J Am Statis Assoc1971; 66: 484–91.
26.
MoroniM., WillinghamM., BeguinotL.EGF-R antisense RNA blocks expression of the epidermal growth factor receptor and suppresses the transforming phenotype of a human carcinoma cell line.J Biol Chem1992; 267: 2712–22.
27.
HiraoT., SawadaH., KoyamaF.Antisense epidermal growth factor receptor delivered by adenoviral vector blocks tumor growth in human gastric cancer.Cancer Gene Therapy1999; 6: 423–7.
28.
HuangS.M., HarariP.M.Epidermal growth factor receptor inhibition in cancer therapy: biology, rationale and preliminary results.Invest New Drugs1999; 17: 259–69.
