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Increased Expression of Valosin-Containing Protein (p97) Is Correlated With Disease Recurrence in Follicular Thyroid Cancer

¹ Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
² Department of Pathology (C3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
³ Division of Surgery, Kuma Hospital, 8-2-35 Shimoyamate, Chuo, Kobe, 650-0011, Japan

Correspondence: Address correspondence and reprint requests to: Yasuhiko Tomita, MD; E-mail: yt{at}molpath.med.osaka-u.ac.jp.

Background: Valosin-containing protein (VCP) is involved in the ubiquitin/proteasome-degradation pathway, which works in proliferation and antiapoptosis in human cancer cells. Our previous study showed that VCP expression levels correlated with the recurrence and prognosis of several human cancers, such as hepatocellular carcinoma, gastric carcinoma, and colorectal carcinoma. In this study, the correlation of VCP expression with the prognosis of differentiated thyroid carcinoma was examined.

Methods: VCP expression in 332 patients who underwent operation for differentiated thyroid carcinoma—257 with papillary thyroid carcinoma and 75 with follicular thyroid carcinoma (FTC)—was analyzed by immunohistochemistry. The staining intensity in tumor cells was categorized as weaker than (low expression), equal to (intermediate expression), or stronger than (high expression) that in endothelial cells in noncancerous tissue.

Results: One hundred ten (33.5%) cases showed low VCP expression, 117 (28.0%) showed intermediate expression, and 101 (30.8%) showed high expression. VCP expression significantly correlated with histological subtype (P < .05) and lymph node metastasis (P < .01). However, it correlated with neither any clinicopathologic factor nor prognosis in papillary thyroid carcinoma. VCP expression correlated with extrathyroidal extension (P < .05), pT classification (P < .05), and lymph node metastasis (P < .01) in FTC. Patients with low VCP expressing FTC showed better disease-free and overall survival rates than those with intermediate or high expression (P < .01 and P < .05, respectively). Multivariate analysis revealed VCP expression and extracapsular extension to be independent prognostic factors for disease-free survival in cases of FTC.

Conclusions: The prognostic utility of VCP expression in FTC was demonstrated.

Key Words: Valosin-containing protein • Prognosis • Follicular thyroid carcinoma • Metastasis

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