Loading…
Serum Bone Sialoprotein in Patients with Primary Breast Cancer Is a Prognostic Marker for Subsequent Bone Metastasis
Bone sialoprotein (BSP) is a noncollagenous bone matrix protein that is important for both mineralization and cell-cell interactions. Tissue studies in primary breast cancers have shown that immunohistochemical expression of BSP is associated with a high incidence of bone metastases in the course of...
Saved in:
Published in: | Clinical cancer research 1999-12, Vol.5 (12), p.3914-3919 |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Bone sialoprotein (BSP) is a noncollagenous bone matrix protein that is important for both mineralization and cell-cell interactions.
Tissue studies in primary breast cancers have shown that immunohistochemical expression of BSP is associated with a high incidence
of bone metastases in the course of the disease. We used a RIA to investigate the importance of serum BSP as a marker for
subsequent bone metastases. Between 1994 and 1996, preoperative blood samples were collected from 388 consecutive patients
with nonmetastatic breast cancer and from 30 control patients with benign breast disease. Serum BSP concentrations were measured
in a blinded fashion by RIA. The cutoff for elevated serum BSP values was 24 ng/ml, i.e. , two SDs above the normal mean value. Serum BSP was correlated with the risk of metastasis and analyzed with regard to its
prognostic value. After a median follow-up period of only 20 months, 28 patients had developed metastases. Fourteen patients
had bone metastases only, 9 visceral metastases only, and 5 a combination of osseous and visceral metastases. Of the 19 women
with skeletal metastases, 17 had preoperative serum BSP values in excess of 24 ng/ml (median BSP values: 48.3 ng/ml for isolated
metastatic bone disease, 30.6 ng/ml for combined metastases), whereas none of the women with visceral metastases only had
elevated serum BSP concentrations (median BSP value: 12.3 ng/ml). The median serum BSP value in the control group (benign
breast disease) was 8.8 ng/ml serum BSP; levels correlated with the size of the primary tumor, but not with any other prognostic
factors. Using a multivariate regression analysis, serum BSP was found to be the most important independent prognostic factor
for the development of skeletal metastasis ( P < 0.001; relative risk, 94); its specificity was 96.7%, and its sensitivity was 89.5%. Our study shows that patients with
preoperatively elevated serum BSP levels are at high risk of subsequent bone metastases in the first years after primary surgery.
The mechanism of BSP in the pathogenesis of skeletal metastases is unclear. Because BSP contains an integrin recognition sequence,
its expression in tumor cells may facilitate their adhesion to the bone surface. However, it is possible that a proportion
of circulation BSP is derived from normal or tumor-induced bone turnover. Breast cancer patients with elevated serum BSP levels
may benefit from osteoprotective adjuvant therapy with bisphosphonates. |
---|---|
ISSN: | 1078-0432 1557-3265 |