c-erbB-2 is confirmed as a new independent, functional prognostic parameter for overall survival in gastric cancer, even when a panel of invasion-related factors, including the strong prognostic parameter PAI-1, are considered. The significant correlation of p185 with several tumor-associated proteases supports the hypothesis that c-erbB-2 is a promoter of invasion and metastasis. This strongly suggests that c-erbB-2 may be a promising target for anti-invasive therapy in gastric cancer.

It is unclear whether disseminated tumour cells detected in bone marrow in early stages of solid cancers indicate a subclinical systemic disease component determining the patient's fate or simply represent mainly irrelevant shed cells. Moreover, characteristics differentiating high and low metastatic potential of disseminated tumour cells are not defined. We performed repeated serial bone marrow biopsies during follow-up in operated gastric cancer patients. Most patients with later tumour relapse revealed either an increase or a constantly high number of tumour cells. In contrast, in patients without recurrence, either clearance of tumour cells or negative or low cell counts were seen. Urokinase plasminogen activator (uPA)-receptor expression on disseminated tumour cells was significantly correlated with increasing tumour cell counts and clinical prognosis. These results demonstrate a systemic component in early solid cancer, indicated by early systemically disseminated tumour cells, which may predict individual disease development.

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Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.

PAI-1, uPA, and uPA-R are new functional risk factors reflecting clinical prognosis. In particular, PAI-1 is a new independent variable for the identification of patients at high risk after tumor resection. Our results support the hypothesis that the uPA system probably is of general importance for prognosis of patients with malignant disease, indicating an individual tumor's capacity for invasion and metastasis.