Prognostic impact of circulating tumor cells in patients with ampullary cancer

J Cell Physiol. 2018 Jun;233(6):5014-5022. doi: 10.1002/jcp.26353. Epub 2018 Jan 4.

Abstract

Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

Keywords: ampullary cancer; circulating tumor cells; prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ampulla of Vater / pathology*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / therapy
  • Case-Control Studies
  • Centromere / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leukocyte Common Antigens / blood
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / chemistry
  • Neoplastic Cells, Circulating / pathology*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Leukocyte Common Antigens
  • PTPRC protein, human