Impact of epidermal growth factor (EGF) radioreceptor analysis on long-term survival of gastric cancer patients.

BACKGROUND: The EGF receptor/ligand system seems to be involved in the regulation of gastric mucosa proliferation and progression of gastric carcinomas. PATIENTS AND METHODS: EGF receptor levels were quantitatively determined in 47 gastric carcinomas by 125J [EGF] radioreceptor assays in membrane preparations of tumor samples or corresponding adjacent mucosa. Specific receptor binding was determined by the analysis of displacement curves by non-linear least-square regression analysis using an estimated model of 'goodness of fit'. RESULTS: Increased EGF receptor binding was observed in gastric carcinomas (mean +/- SEM: 11.87 +/- 1.9 fmol/mg protein) in comparison to adjacent normal gastric mucosa ( 5.28 +/- 1.0 fmol/mg protein, p = 0.003). Elevated EGF receptor levels were especially found in more invasive T3/4 carcinomas, tumors with positive lymph nodes, advanced UICC III carcinomas, undifferentiated tumors, carcinomas of the diffuse-type according to Lauren's classification and gastric carcinomas localized distal from the cardia. In histopathologically normal appearing gastric mucosa, EGF-receptor levels were significantly decreased relative to corresponding tumor samples from advanced UICC stages (UICC I vs UICC I/II: p = 0.008) or tumors with low levels of differentiation (G2 vs G3: p = 0.028). Overall survival was significantly reduced in patients with advanced gastric carcinomas according to UICC classification (UICC III vs UICC I/II: 18.8 vs 45.5 months, p = 0.016). A subgroup analysis of gastric carcinomas localized distal from the cardia indicated, that increased EGF-receptor levels were an independent indicator of poor prognosis as determined by univariate (p = 0.020) and multivariate analysis (p = 0.042). CONCLUSION: Gastric carcinomas with increased EGF receptors might be a possible target for anticancer strategies blocking the EGF receptor/ligand pathway.

Increased epidermal growth factor receptors in gastric carcinomas.

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.

Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas.

The epidermal growth factor (EGF) and alpha-tumor growth factor are mitogenic proteins which bind to the EGF-receptor and may play a role in carcinogenesis or tumor progression. Our study investigated whether colorectal carcinomas and adenomas express altered levels of EGF-receptors or overproduce EGF-like activity by comparing histologically normal mucosa to carcinomas resected from the same patients. EGF-receptors were characterized by radioligand binding studies. Carcinomas contained unchanged or decreased levels of EGF-receptors in 13/16 and moderately increased levels in 3/16 patients as compared to normal mucosa. Adenomas obtained from 2 patients with familial polyposis coli and from a third patient with a coincident carcinoma had similar numbers of EGF-receptors as normal mucosa. EGF-like growth factors, in contrast, were significantly elevated in carcinoma extracts as compared to extracts from normal mucosa of the same patients. Adenomas did not contain elevated levels of EGF-like activity. We conclude that increased expression of EGF-receptors is infrequent in colonic adenocarcinomas. Increased production of EGF-like growth factors may frequently occur but seems to be associated with tumor progression rather than with premalignant lesions as represented by adenomas.