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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2004.05.012 on January 12, 2004

Annals of Surgical Oncology 11:165-172 (2004)
© 2004 Society of Surgical Oncology
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ORIGINAL ARTICLES

Increased Expression of Valosin-Containing Protein (p97) is Associated With Lymph Node Metastasis and Prognosis of Pancreatic Ductal Adenocarcinoma

Shinji Yamamoto, MD, Yasuhiko Tomita, MD, Yoshihiko Hoshida, MD, Hiroaki Nagano, MD, Keizo Dono, MD, Koji Umeshita, MD, Masato Sakon, MD, Osamu Ishikawa, MD, Hiroaki Ohigashi, MD, Shoji Nakamori, MD, Morito Monden, MD and Katsuyuki Aozasa, MD

From the Departments of Surgery and Clinical Oncology (SY, HN, KD, KU, MS, SN, MM) and Pathology (YT, YH, KA), Osaka University Graduate School of Medicine, Suita; and Department of Surgery (OI, HO), Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.

Correspondence: Address correspondence and reprint requests to: Shoji Nakamori, MD, Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2–2 Yamadaoka, Suita, Osaka 565–0871, Japan; Fax: 81-6-6879-3259; E-mail: nakamori{at}surg2.med.osaka-u.ac.jp

Background: Valosin-containing protein (VCP, also known as p97) exhibits antiapoptotic function and metastasis by activation of nuclear factor kappa-B signaling pathway. Our previous study showed that VCP expression level correlated with prognosis of hepatocellular and gastric carcinoma. In the present study, association of VCP expression with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma (PDAC) was examined.

Methods: VCP expression in 83 patients (46 males and 37 females) of ages ranging from 43 to 80 (median, 66) years who had undergone curative surgery for primary PDAC was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker or equal to (low expression) or stronger (high expression) than that in noncancerous ductal tissue.

Results: Thirty-two tumors (38.6%) and 51 tumors (61.4%) were classified as low-VCP-expressing and high-VCP-expressing tumors, respectively. VCP expression correlated significantly with lymph node metastasis (P < .01) but not with various clinicopathologic factors, including age, gender, and histologic differentiation. Multivariate analysis revealed VCP expression as an independent prognosticator for both disease-free and overall survival, along with histologic differentiation, T stage of pathologic tumor-node-metastasis (pTNM) classification, and lymph node metastasis. Furthermore, VCP expression was a prognosticator for disease-free and overall survival in each relatively early stage (I or II) and advanced stage (III) group of pTNM classification.

Conclusions: Our results indicate the potential usefulness of VCP expression as a marker of metastasis and overall prognosis of PDAC.

Key Words: Pancreatic adenocarcinoma • Prognosis • Valosin-containing protein • Lymph node metastasis




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