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Elevated Expression of Valosin-Containing Protein (p97) Is Associated with Poor Prognosis of Prostate Cancer

¹ Departments of Pathology, ² Surgery and Clinical Oncology, and ³ Urology, Osaka University Graduate School of Medicine, Osaka, Japan, and ⁴ Division of Urology, Osaka National Hospital, Osaka, Japan

Purpose: Valosin-containing protein (VCP) has been shown to be associated with metastasis and prognosis in human cancers. In the present study, the correlation of VCP with recurrence and prognosis in patients with prostate cancer (PCA) receiving conservative therapy was examined.

Experimental Design: VCP expression was analyzed immunohistochemically in 136 patients ranging from 46 to 92 years (median, 72 years), who received conservative therapy, including androgen deprivation, radiotherapy, or watchful waiting. Staining intensity of tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 10 patients.

Results: Thirty-two cases (23.5%) showed level 1 and 100 (76.5%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCPmRNA expression in level 2 (n = 5) than level 1 cases (n = 5; P < 0.05). A significant difference was observed between VCP level 1 and 2 patients in the positive rate for the digital rectal examination (P < 0.01), serum prostate-specific antigen level (P < 0.0001), cancer volume (P < 0.0001), Gleason score (P < 0.0001), stage (P < 0.0001), and progression-free and overall survival (P < 0.0001 for both). Multivariate analysis revealed VCP expression level, serum prostate-specific antigen level, and Gleason score to be independent prognosticators for progression-free and overall survival. Progression of PCA was found in 9.4% of level 1 but in 64% of level 2 patients.

Conclusions: PCA with level 1 VCP expression could be treated conservatively.

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