Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only

Niki A. Ottenhof, Folkert H M Morsink, Fiebo Ten Kate, Cornelis J F Van Noorden, G. Johan A Offerhaus

Research output: Contribution to journalArticle


Background Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival rate of >5% and an average survival of only 6 months. Although advances have been made in understanding the pathogenesis of PDAC in the last decades, overall survival has not changed. Various clinicopathological and immunohistological variables have been associated with survival time but the exact role that these variables play in relation to survival is not clear. Methods and results To examine how the variables affected survival independently, multivariate analysis was conducted in a study group of 78 pancreatic ductal adenocarcinomas. The analysis included clinicopathological parameters and protein expression examined by immunohistochemistry of p53, Smad4, Axl, ALDH, MSH2, MSH6, MLH1 and PMS2. Lymph node ratio ≥0.2 (p00.004), tumor free resection margins (p00.044) and Smad4 expression (p00.004) were the only independent prognostic variables in the multivariate analysis. Expression of the other proteins examined was not significantly related to survival. Conclusions Discrepancieswith other studies in this regard are likely due to differences in quantification of immunohistochemical staining and the lack of multivariate analysis. It underscores the importance to standardize the methods used for the application of immunohistochemistry in prognostic studies.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalCellular Oncology
Issue number2
StatePublished - Apr 2012
Externally publishedYes



  • Immunohistochemistry
  • Long term survival
  • Lymph node ratio
  • Pancreatic ductal adenocarcinoma
  • Prognosis
  • Resection margin
  • Smad4

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology
  • Medicine(all)

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