PROGNOSTIC RELEVANCE OF UROKINASE PLASMINOGEN-ACTIVATOR DETECTION IN MICROMETASTATIC CELLS IN THE BONE-MARROW OF PATIENTS WITH PRIMARY BREAST-CANCER

Patients with an elevated level of urokinase plasminogen activator (uP A) in breast cancer tissue have an adverse prognosis. This study evalu ated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from bo th iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodi es: 2E11, which detects TAG 12-a tumour-associated glycoprotein typica lly expressed by almost all breast cancer cells-and the anti-uPA antib ody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) deve loped metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Pa tients with uPA-positive cells in bone marrow (n = 98, 35%) had a sign ificantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patie nts positive for both markers (29.5 months), followed by those who wer e uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant sys temic therapy. For the first time, it was possible to evaluate an impo rtant qualitative parameter involved in the process of breast cancer m etastases.