Prognostic Role of a Multimarker Analysis of Circulating Tumor Cells in Advanced Gastric and Gastroesophageal Adenocarcinomas

Oncology. 2015;89(5):294-303. doi: 10.1159/000437373. Epub 2015 Aug 28.

Abstract

Objective: We aimed to assess the prognostic value of circulating tumor cells (CTC) in patients with advanced gastric and gastroesophageal adenocarcinomas.

Methods: The presence of CTC was evaluated in 62 patients with advanced gastric and gastroesophageal adenocarcinomas before systemic therapy and at follow-up through immunomagnetic enrichment for mucin 1- and epithelial cell adhesion molecule (EpCAM)-positive cells, followed by real-time RT-PCR of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5.

Results: The patients were stratified into groups according to CTC detection (CTC negative: with all marker genes negative; CTC positive: with at least 1 of the marker genes positive). Patients who were CTC positive at baseline had a significantly shorter median progression-free survival (PFS; 3.5 months, 95% CI: 2.9-4.2) and overall survival (OS; 5.8 months, 95% CI: 4.5-7.0) than patients lacking CTC (PFS 10.7 months, 95% CI: 6.9-14.4, p<0.001; OS 13.3 months, 95% CI: 8.0-18.6, p=0.003). Alterations in the marker profile during the course of chemotherapy were not predictive of clinical outcome or response to therapy. Yet, a favorable clinical response depended significantly on CTC negativity (p=0.03).

Conclusion: Our data suggest that the presence of CTC is a major predictor of outcome in patients with gastric and gastroesophageal malignancies.

MeSH terms

  • Adenocarcinoma / pathology*
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Carcinoembryonic Antigen / metabolism
  • Cell Adhesion Molecules / metabolism
  • Disease-Free Survival
  • Epithelial Cell Adhesion Molecule
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Female
  • GPI-Linked Proteins / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Male
  • Middle Aged
  • Mucin-1 / metabolism
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survivin

Substances

  • Antigens, Neoplasm
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • CEACAM5 protein, human
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • GPI-Linked Proteins
  • Inhibitor of Apoptosis Proteins
  • Mucin-1
  • Survivin