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 norm al and neoplastic cell proliferation. The role of EGF, the EGF recepto r, and c-erbB-2 in human gastric cancer is reviewed on the basis of se veral reports, which have been mainly oriented toward their clinical s ignificance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric canc er is correlated with the degree of gastric wall invasion and lymph no de metastasis. The 5-year survival of patients with EGF-positive tumor s is worse than that of patients with EGF-negative tumors. The presenc e of EGF in human gastric cancer may therefore represent a higher mali gnant potential. Fifteen percent of gastric cancers (n = 352) were als o shown to be positive for both EGF and the EGF receptor immunohistoch emically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibi ting 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 a ggressiveness, although gene amplification has occurred only to a smal l 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 tha n those with c-erbB-2-negative tumors. Selective blockade of the EGF r eceptor and c-erbB-2 from their ligands with monoclonal antibodies (Mo Abs) inhibits the growth of human gastric cancer xenografts. These MoA bs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.