Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis

Purpose: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB 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 (T1-2 versus T3-4, 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.