Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer: a Single Institution Analysis

Pathol Oncol Res. 2019 Jul;25(3):1059-1066. doi: 10.1007/s12253-018-0464-y. Epub 2018 Sep 5.

Abstract

We investigated the expression patterns of Ki67 and p53 in metastatic pancreatic adenocarcinomas and analyzed their relationship with disease progression-free survival (PFS) and overall survival (OS) in the overall study population and in patients treated with a gemcitabine-containing chemotherapy versus FOLFIRINOX chemotherapy. Patients with histologically confirmed stage IV adenocarcinoma of the pancreas treated at AUBMC were included after obtaining institutional review board approval (IRB ID: IM.ST.05). The ROC was plotted to identify the threshold Ki-67, p53 and CA19-9 value for disease progression, the identified value was further used in Kaplan Meier curves to compare PFS for both groups (gemcitabine versus FOLFIRINOX). A value of p < 0.05 was considered significant in all analyses. On univariate analysis, patients who had a Ki-67 > 12.5% or a p53 > 15% had significantly shorter PFS (p = 0.034 and p = 0.016, respectively). This effect was restricted to Gemcitabine or gemcitabine-combination treated patients. A decrease in CA19-9 levels 6-8 weeks after chemotherapy of >58% had significantly longer PFS (p = 0.027). On multivariate analysis after controlling for grade, age and P53, Ki-67 remained significant, for every one unit increase in Ki-67 the progression risk increases by 1.017 times. Our study highlights the negative impact of high P53 expression and Ki67 proliferation index on PFS in patients with metastatic pancreatic cancer.

Keywords: CA19–9; Ki67; P53; Pancreatic cancer; Prognosis.

Publication types

  • Clinical Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Irinotecan / administration & dosage
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Oxaliplatin / administration & dosage
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Fluorouracil
  • Gemcitabine