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Expression Level of Valosin-Containing Protein (p97) Is Correlated With Progression and Prognosis of Non-Small-Cell Lung Carcinoma

From the Departments of Surgery and Clinical Oncology (ShY, MM) and Pathology (YT, YH, NI, KA), Osaka University Graduate School of Medicine, Suita, Japan; and the Divisions of Pathology (SaY) and Surgery (KI), National Kinki Chuo Hospital, Osaka, Japan.

Correspondence: Address correspondence and reprint requests to: Yasuhiko Tomita, MD, Department of Pathology (C3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka 565-0871, Japan; Fax: 81-6-6879-3719; E-mail: yt{at}molpath.med.osaka-u.ac.jp

Background: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptosis and metastasis via activation of a nuclear factor-B signaling pathway. Our previous study showed that the VCP expression level correlated with the disease recurrence rate and prognosis of patients with hepatocellular carcinoma and gastric carcinoma. This study was designed to evaluate the prognostic significance of VCP expression in non-small-cell lung carcinoma (NSCLC).

Methods: VCP expression in 207 patients with NSCLC (133 men and 74 women) aged 35 to 78 years (median, 62 years) was examined by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker than (level 1) or equal to or stronger than (level 2) that in endothelial cells.

Results: Sixty-nine (33.8%) cases showed level 1 and 135 (66.2%) showed level 2 VCP expression. The frequency of the following was higher in patients with level 2 expression than in those with level 1 expression: male sex (P < .01), histological subtype of squamous cell carcinoma (P < .05), and smoking (P < .05). Patients with level 2 expression had poorer disease-free and overall survival rates (P < .05 and P < .01, respectively) than those with level 1 expression. Multivariate analysis revealed VCP expression and pathologic T (pT) and pN classifications to be independent prognostic factors for both disease-free and overall survival and showed vascular invasion to be an independent prognostic factor for overall survival. VCP level was a prognosticator for overall survival in both the early (pT1) and advanced (pT2–3) group of the pT classification (P < .05 for both).

Conclusions: The prognostic significance of VCP expression in NSCLC was demonstrated.

Key Words: Valosin-containing protein • Prognosis • Non-small-cell lung carcinoma • Survival

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