RELATIONSHIP OF C-ERBB-2 PROTEIN EXPRESSION AND GENE AMPLIFICATION TO INVASION AND METASTASIS IN HUMAN GASTRIC-CANCER

Background. Amplification and/or overexpression of the C-erbB-2 gene has been demonstrated in breast and gastric cancer and is thought to be involved in the process of gastric cancer metastasis. Methods. The expression of C-erbB-2 protein in human gastric cancer was examined by immunohistochemistry and amplification of the C-erbB-2 gene by Southern blot hybridization. Results. C-erbB-2 protein was located on the cell membrane of cancer cells in formalin-fixed, paraffin-embedded sections. Fourteen percent of specimens were positive for C-erbB-2, and no positive reaction was evident in noncancerous tissue. The presence of C-erbB-2 in gastric cancer was correlated with the depth of invasion, histologic type, growth pattern, and presence of liver metastasis. C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01). The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01). Patients with C-erbB-2-positive tumors had poorer survival rates those with C-erbB-2-negative tumors in the early stages (P < 0.001), but not in the advanced stages. Amplification of the C-erbB-2 gene was detected at the primary site and in metastatic nodes in the same case, and expression of the protein was also evident. Conclusions. The expression and/or gene amplification of C-erbB-2 is related to invasion and nodal involvement in differentiated adenocarcinoma of the human stomach.