Increased expression of valosin-containing protein (p97) is associated with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma

Ann Surg Oncol. 2004 Feb;11(2):165-72. doi: 10.1245/aso.2004.05.012.

Abstract

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.

MeSH terms

  • Adenosine Triphosphatases
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle Proteins / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Japan / epidemiology
  • Lymphatic Metastasis / diagnosis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • Valosin Containing Protein

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein