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Soluble ErbB3 Levels in Bone Marrow and Plasma of Men with Prostate Cancer

Authors' Affiliations: Departments of ¹ Molecular Pathology, ² Genitourinary Medical Oncology, ³ Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center; and ⁴ Department of Medicine, Baylor College of Medicine, Houston, Texas

Requests for reprints: Sue-Hwa Lin, Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-794-1559; Fax: 1-713-794-4672; E-mail: slin{at}mdanderson.org.

Purpose: Prostate cancer tends to metastasize to bone and induce osteoblastic lesions. We identified a soluble form of ErbB3 (sErbB3), p45-sErbB3, in bone marrow supernatant from men with prostate cancer bone metastasis and showed that p45-sErbB3 enhances bone formation. We aimed to understand clinical implications of sErbB3 by establishing an ELISA to detect sErbB3 levels in bone marrow and plasma samples.

Experimental Design: We did ELISAs on marrow from 108 men [34 with androgen-dependent disease, 30 with androgen-independent disease (AI) but negative bone scan (AI/BS–), and 44 with AI and positive bone scan (AI/BS+)], sequential marrow from 5 men during treatment, plasma from 52 men before and after docetaxel treatment, and plasma from 95 men ages 70 years old without prostate cancer.

Results: Some men with clinically detectable bone metastasis had high sErbB3 levels. Within the AI/BS– group, higher sErbB3 levels seemed to yield lower rates of bone metastasis. In the AI/BS+ group, detectable bone metastases took longer to appear in men with higher sErbB3 levels than in men with lower sErbB3 levels (median, 82 versus 41 months). However, high sErbB3 levels did not confer survival benefit after metastasis development. Among men with metastatic progression in bone, docetaxel treatment reduced plasma sErbB3 (P < 0.0001) but did not affect bone-specific alkaline phosphatase (P = 0.206) or prostate-specific antigen (P = 0.906). sErbB3 was also detected in men without prostate cancer.

Conclusions: The apparent correlation between higher sErbB3 levels and longer time to bone metastasis suggests that sErbB3 participates in progression in bone of prostate cancer.