P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment

Pathol Res Pract. 2016 Aug;212(8):726-34. doi: 10.1016/j.prp.2016.06.001. Epub 2016 Jun 8.

Abstract

In pancreatic cancer there is a need for prognostic risk stratification and subsequent therapy strategies. Molecular analysis has shown in different cancers that variation in clinical behavior can be associated with specific alterations. The cell cycle regulators p16 and p53 belong to the most often alterated genes in pancreatic ductal adenocarcinoma (PDAC). We analyzed protein expression of p16, p53 and Ki67 by immunohistochemistry in 162 tumours of the CONKO-001 trial that investigated the role of adjuvant gemcitabine in pancreatic cancer patients. We could show that high proliferation of tumours and strong and consistent nuclear p53 expression by tumour cells is associated with a worse disease-free survival and overall survival in the overall study population. However, stratified analysis according to treatment arm revealed that the effect of deregulated p53 expression and high Ki67 expression was restricted to the disease free survival of patients treated with adjuvant gemcitabine. In multivariable survival analysis, p53 did not retain its prognostic status. Our study supports the important role of p53 and Ki67 expression in PDAC. They provide prognostic information in patients with adjuvant gemcitabine treatment and may contribute to treatment decision. However, these results should be validated in further studies.

Keywords: carcinoma; gemcitabine; ki67; p16; p53; pancreas.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Chemotherapy, Adjuvant
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Survival Rate
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation

Substances

  • Antimetabolites, Antineoplastic
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • P16 protein, human
  • Tumor Suppressor Protein p53
  • Deoxycytidine
  • gemcitabine