SummaryTo test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P < 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P < 0.001), and serum β 2 -microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P < 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P < 0.001, logrank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.

Patients with an elevated level of cathepsin D in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of cathepsin D detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both anterior iliac crests in 290 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: BM2, which detects tumour-associated glycoprotein TAG 12, which is typically expressed by almost all breast cancer cells, and the anti-cathepsin D antibody. 67 of 149 BM2-positive women (45%) developed metastatic disease (median follow-up time: 69 months). Of these, 15 were cathepsin D-positive (22%). Patients with cathepsin D-positive cells in bone marrow (n = 26; 9%) had a significantly shorter metastasis-free interval (38 months) compared with women who were cathepsin D-negative (64.5 months). The worst prognosis was seen in patients positive for both markers (30.5 months), followed by those who were cathepsin D-negative and BM2-positive (48 months). The detection of cathepsin D on disseminated tumour cells characterises a subgroup of patients with a poorer prognosis who should undergo more aggressive adjuvant systemic therapy.

In 95% of patients with primary breast cancer, the extent of metastases cannot be proven by conventional methods. Nevertheless, more than 50% of these patients have a relapse within five years. To improve the predictive value for recurrency, we examined bone marrow aspirates of 128 patients with primary breast cancer. Bone marrow aspirates from 2-6 sites of the skeleton (iliac crest and sternum) were taken as well as biopsies for histological examination. The immunohistochemical studies were carried out on interphase smears and stained with cytoceratin antibodies (PKK 1) and antibodies against tumor-specific antigen TAG 12 (12 H 12). All patients were screened for distant metastases (X-ray, ultrasound, bone scan). Tumor cells and micrometastases in bone marrow were detected in 41 patients (32%). Their presence was correlated to other prognostic factors (tumor size, lymph node status, oestrogen/progesterone receptors). The median duration of follow-up was 39.5 months. 14 patients (45%) in the tumor cell positive group relapsed, compared to only 4 out of 36 patients in the tumor cell negative group. In 29% we found bone metastases. The relapse free interval was shorter for patients with micrometastases (8 vs. 15.8 months). The presence of tumor cells in bone marrow aspirates detected at the time of primary surgery, is a useful prognostic factor and a good predictor of metastases and may help in selecting patients for systemic adjuvant treatment.