In an attempt to evaluate the relationship between c-erbB-2 expression and/or gene amplification, DNA ploidy and morphology, wall penetration, lymphatic permeation, and vascular invasion, we studied a series of 87 primary gastric carcinomas and their respective metastases (n = 335) using immunohistochemistry and performed DNA analysis of 30 primary tumors and 10 metastases from eight cases. Flow cytometry of fresh or frozen material was performed in 79 primary tumors. Five out of 87 primary tumors (5.7%) and 17 out of 335 lymph node metastases (5.1%) showed unequivocal membrane immunostaining for c-erbB-2. Seven out of 30 primary tumors (23.3%) showed gene amplification while amplification was identified in four out of 10 metastases (40.0%) from three patients. Eight tumors (9.2%) showed c-erbB-2 protein immunoreactivity, gene amplification, or both. One of these cases showed c-erbB-2 protein immunoreactivity only in the metastatic deposits, while gene amplification could be identified in the primary tumor. Three primary tumors showed gene amplification, but immunoreactive cells could not be identified. In no case was protein overexpression identified in the absence of gene amplification. Five cases with c-erbB-2 expression/amplification were well/moderately differentiated, and all the eight cases with c-erbB-2 expression/amplification disclosed aggressive features. Lymphatic permeation/lymph node metastases were found in all the cases and seven cases showed vascular invasion as well. In one case, there was also a liver metastasis. Two cases were early gastric carcinomas (T1sm) showing lymphatic permeation/nodal metastases and venous invasion. Six cases were aneuploid.(ABSTRACT TRUNCATED AT 250 WORDS)