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

• Published in: Annals of oncology Vol. 19; no. 2; pp. 308 - 314
• Main Authors: Alarmo, E.-L., Korhonen, T., Kuukasjärvi, T., Huhtala, H., Holli, K., Kallioniemi, A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2008; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Analysis of Variance; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - analysis; bone metastasis; Bone Morphogenetic Protein 7; bone morphogenetic proteins; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Bone Neoplasms - genetics; Bone Neoplasms - mortality; Bone Neoplasms - secondary; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - secondary; Carcinoma, Lobular - genetics; Carcinoma, Lobular - mortality; Carcinoma, Lobular - secondary; Cohort Studies; Diseases of the osteoarticular system; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; invasive ductal carcinoma; invasive lobular carcinoma; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Pharmacology. Drug treatments; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Survival Analysis; Time Factors; tissue microarray; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Tumors; Tumors of striated muscle and skeleton; invasive ductal carcinoma; immunohistochemistry; bone metastasis; invasive lobular carcinoma; tissue microarray; bone morphogenetic proteins; Immunohistochemistry; Ductal carcinoma; Diseases of the osteoarticular system; Breast cancer; Malignant tumor; Gene expression; Mammary gland diseases; Breast carcinoma; Anatomic pathology; Bone metastasis; Bone morphogenetic protein; Tissue microarrays; Breast metastasis; Invasive cancer; Cancer; Bone morphogenetic protein 7
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdm453

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.