Prognostic significance of PUMA in pancreatic ductal adenocarcinoma

J Int Med Res. 2012;40(6):2066-72. doi: 10.1177/030006051204000603.

Abstract

Objectives: To investigate retrospectively whether alterations of p53 upregulated mediator of apoptosis (PUMA) protein levels and somatic mutations of the PUMA gene are characteristic of pancreatic ductal adenocarcinoma (PDAC).

Methods: Immunohistochemical analyses of PUMA were performed in pancreatic tumour tissue samples, and paired normal pancreatic tissue samples, from patients with PDAC. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assay.

Results: A total of 70 patients with PDAC had samples available; 49 cases (70.0%) had high PUMA protein levels. PUMA was not detected in paired normal tissue samples. Significantly higher levels of PUMA protein were detected in low-grade tumours (tumour -node-metastasis stages I and II), compared with higher grade (stage III) tumours. Of the PDAC cases, the mean apoptosis index value for PUMA-positive specimens was significantly higher than that for PUMA-negative specimens. Overall survival was significantly associated with PUMA immunoreactivity.

Conclusions: High levels of PUMA in PDAC tumour cells suggest that PUMA expression may play a role in pancreatic tumourigenesis.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Retrospective Studies

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Proto-Oncogene Proteins