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Expression Level of Valosin-Containing Protein Is Strongly Associated With Progression and Prognosis of Gastric Carcinoma

From the Departments of Surgery and Clinical Oncology, and Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.

Address reprint requests to Yasuhiko Tomita, MD, Department of Pathology (C3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka 565-0871, Japan; email: yt{at}molpath.med.osaka-u.ac.jp.

Purpose: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined.

Patients and Methods: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells.

Results: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P < .0001), undifferentiated histologic subtype (P < .05), presence of vascular and lymphatic invasion (P < .0001 for both), presence of lymph node metastasis (P < .0001), deep tumor invasion (P < .0001), and poorer disease-free and overall survivals (P < .0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P < .01 and P < .05, respectively) and advanced (pT2–4; P < .05 for both) group of pathologic tumor-node-metastasis system classification.

Conclusion: The prognostic significance of VCP expression level in GC was demonstrated.

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