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.


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).


CONCLUSIONS
Gastric carcinomas with increased EGF receptors might be a possible target for anticancer strategies blocking the EGF receptor/ligand pathway.
Kopp
R
R
Department of Surgery, Klinikum Grosshadern, Univresity of Munich, Berlin, Germany. rkopp@med.gch.uni-muenchen.de
Ruge
M
M
Rothbauer
E
E
Cramer
C
C
Kraemling
H J
HJ
Wiebeck
B
B
Schildberg
F W
FW
Pfeiffer
A
A
D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D009367:Neoplasm Staging; D011869:Radioligand Assay; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors