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Expression of Valosin-Containing Protein in Colorectal Carcinomas as a Predictor for Disease Recurrence and Prognosis

¹ Departments of Surgery and Clinical Oncology and ² Pathology, Osaka University Graduate School of Medicine, Osaka, and ³ Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan

Purpose: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-B signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma.

Experimental Design: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35–84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci.

Results: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T_1–2 versus T_3–4, P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively).

Conclusions: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.

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