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Annals of Oncology Advance Access published online on September 24, 2007
Annals of Oncology, doi:10.1093/annonc/mdm453
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© 2007 European Society for Medical Oncology

Bone morphogenetic protein 7 expression associates with bone metastasis in breast carcinomas

E. -L. Alarmo1, T. Korhonen2, T. Kuukasjärvi3, H. Huhtala4, K. Holli5 and A. Kallioniemi1,*

1 Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital
2 Department of Palliative Medicine
3 Department of Pathology, Tampere University Hospital
4 School of Public Health
5 Medical School, University of Tampere, Tampere, Finland

* Correspondence to: Prof. A. Kallioniemi, Institute of Medical Technology, FIN-33014 University of Tampere, Finland. Tel: +358-3-31164125; Fax: +358-3-31174168; E-mail: anne.kallioniemi{at}uta.fi

Background: We recently showed that bone morphogenetic protein 7 (BMP7) is overexpressed in primary breast tumors. Here we explored the clinical significance of BMP7 expression in breast cancer.

Materials and methods: This study included 483 breast cancer patients with complete clinicopathological information and up to 15 years of follow-up. Samples contained 241 lobular carcinomas, 242 ductal carcinomas, and 40 local recurrences. BMP7 protein expression was determined using immunohistochemistry.

Results: BMP7 was expressed in 47% of the primary tumor samples and 13% of the local recurrences. The primary tumors expressed BMP7 more often than the corresponding local recurrences (P = 0.004). BMP7 expression was dependent on the tumor subtype; 57% of the lobular carcinomas but only 37% of the ductal carcinomas were BMP7 positive (P = 0.0001). BMP7 expression was associated with accelerated bone metastasis formation (P = 0.040), especially in ductal carcinomas (P = 0.033), and multivariate analysis confirmed that BMP7 is an independent prognostic indicator for early bone metastasis development (P = 0.032).

Conclusion: BMP7 is clearly associated with bone metastasis formation and thus might have clinical utility in identification of patients with increased risk of bone metastasis. This is the first time that bone inducing factor BMP7 has been linked to the bone metastasis process in breast cancer.

bone metastasis, bone morphogenetic proteins, immunohistochemistry, invasive ductal carcinoma, invasive lobular carcinoma, tissue microarray

Received for publication July 3, 2007. Revision received August 9, 2007. Accepted for publication August 10, 2007.


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