This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Diel, I. J. Articles by Bastert, G. Search for Related Content PubMed PubMed Citation Articles by Diel, I. J. Articles by Bastert, G.

Serum Bone Sialoprotein in Patients with Primary Breast Cancer Is a Prognostic Marker for Subsequent Bone Metastasis

Departments of Obstetrics and Gynecology [I. J. D., E. F. S., C. G., H. M., G. K., E. B., F. P. A., G. B.], Endocrinology [M. J. S., J. P.], and Anesthesiology [R. C.], University of Heidelberg, 69115 Heidelberg, Germany, and Department of Medical Oncology, Wilhelminenspital, 1160 Vienna, Austria [M. P.]

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.

This article has been cited by other articles:

				P. Garnero New Biochemical Markers of Bone Turnover IBMS BoneKEy, March 1, 2008; 5(3): 84 - 102. [Abstract] [Full Text] [PDF]

				Y. Zheng, H. Zhou, J. R.K. Modzelewski, R. Kalak, J. M. Blair, M. J. Seibel, and C. R. Dunstan Accelerated Bone Resorption, Due to Dietary Calcium Deficiency, Promotes Breast Cancer Tumor Growth in Bone Cancer Res., October 1, 2007; 67(19): 9542 - 9548. [Abstract] [Full Text] [PDF]

				J.-S. Nam, A. M. Suchar, M.-J. Kang, C. H. Stuelten, B. Tang, A. M. Michalowska, L. W. Fisher, N. S. Fedarko, A. Jain, J. Pinkas, et al. Bone Sialoprotein Mediates the Tumor Cell-Targeted Prometastatic Activity of Transforming Growth Factor {beta} in a Mouse Model of Breast Cancer. Cancer Res., June 15, 2006; 66(12): 6327 - 6335. [Abstract] [Full Text] [PDF]

				B. Fohr, C. R. Dunstan, and M. J. Seibel Markers of Bone Remodeling in Metastatic Bone Disease J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5059 - 5075. [Abstract] [Full Text] [PDF]

				N. S. Fedarko, A. Jain, A. Karadag, M. R. Van Eman, and L. W. Fisher Elevated Serum Bone Sialoprotein and Osteopontin in Colon, Breast, Prostate, and Lung Cancer Clin. Cancer Res., December 1, 2001; 7(12): 4060 - 4066. [Abstract] [Full Text] [PDF]

				N. Takahashi, R. Kawanishi-Tabata, A. Haba, M. Tabata, Y. Haruta, H. Tsai, and B. K. Seon Association of Serum Endoglin with Metastasis in Patients with Colorectal, Breast, and Other Solid Tumors, and SuppressiveEffect of Chemotherapy on the Serum Endoglin Clin. Cancer Res., March 1, 2001; 7(3): 524 - 532. [Abstract] [Full Text]

				M. Wuttke, S. Muller, D. P. Nitsche, M. Paulsson, F.-G. Hanisch, and P. Maurer Structural Characterization of Human Recombinant and Bone-derived Bone Sialoprotein. FUNCTIONAL IMPLICATIONS FOR CELL ATTACHMENT AND HYDROXYAPATITE BINDING J. Biol. Chem., September 21, 2001; 276(39): 36839 - 36848. [Abstract] [Full Text] [PDF]