title: Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.
abstract: BACKGROUND
  Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity.
  
  
  METHODS
  Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test.
  
  
  RESULTS
  CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining.
  
  
  CONCLUSIONS
  High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.
authors.affiliation: a Division of Surgical Oncology; Department of Surgery.
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Miriam
authors.initials: M
authors.lastname: Kunkel
authors.forename: David T
authors.initials: DT
authors.lastname: Dicker
authors.forename: Jamal
authors.initials: J
authors.lastname: Joude
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Allen
authors.forename: Avisnata
authors.initials: A
authors.lastname: Das
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.forename: Nabeel E
authors.initials: NE
authors.lastname: Sarwani
authors.forename: Guangfu
authors.initials: G
authors.lastname: Li
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Staveley-O'Carroll
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: CRC, colorectal cancer; CTCsc, circulating tumor cells; Colorectal cancer; EpCAM, epithelial cell adhesion Molecule; circulating tumor cells; liver metastasis; liver volumetry; stage IV; tumor burden