Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer.
The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.
Tokunaga
A
A
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Onda
M
M
Okuda
T
T
Teramoto
T
T
Fujita
I
I
Mizutani
T
T
Kiyama
T
T
Yoshiyuki
T
T
Nishi
K
K
Matsukura
N
N
D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases