Although support from clinical follow-up is still needed, this study demonstrates that, beyond the mere presence of micrometastatic cells in bone marrow, useful prognostic information can be obtained by analysis of additional cell growth markers.

The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.

SummaryWe have examined the cell surface molecule CD44, which is attracting interest because of reports that isoforms are associated with metastasis. The prognostic value of CD44 expression has yet to be assessed for a solid tumour.Benign (59) and malignant (primary 61, metastatic 59) gastric tissues were examined with antibodies directed at epitopes common to known CD44 isoforms. Normal mucosa was CD44 negative. In atrophic gastritis and intestinal metaplasia expression was restricted to the epithelial cells of the basal glands and was positively correlated with an increased leucocyte infiltrate and with the expression of HU\ DR by mucosal cells. These observations suggest a role for chronic inflammation in the induction of CD44 expression on benign mucosa. No such association was observed between inflammatory infiltrate and CD44 expression on gastric tumours.CD44 expression, observed in only 49% of primary tumours, was associated with distant metastases at time of diagnosis and, among 31 curatively resected patients, with tumour recurrence (p~ 0-0014) and increased mortality (p = 0-001) during follow-up averaging 17 months. When we used an antibody directed against the CD44 variant exon 9v, we found a good correlation between the expression of total CD44 and of exon 9v containing isoforms, and 9v expression in primary tumours was significantly and positively associated with tumour recurrence and mortality. Lancet 1993; 3 4 2 :1 0 1 9 -2 2

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.