title: Circulating tumor cells are associated with diffuse spread in stage IV colorectal cancer patients.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States when combining both genders. Circulating tumor cells (CTCs) are a prognostic marker for stage IV CRC patients. We hypothesized that CTC quantity varies among stage IV CRC populations.
  
  
  METHODS
  Blood (7.5 ml) was prospectively collected from 90 stage IV CRC patients. EpCAM(+) CTCs were analyzed with the FDA-approved CellSearch(®) system. CRC tumors were immunohistochemically stained for EpCAM expression. Imaging and clinicopathological data were collected. Statistical analysis was performed using correlation analysis, Kruskal-Wallis, Fisher exact, and log-rank test.
  
  
  RESULTS
  CTCs were detectable in 36/90 (40%) patients. Diffuse CRC metastases were associated with the highest CTC prevalence (24/40 [60%]), in contrast to limited lung (2/19 [11%]) or liver (10/31 [32%]) metastases (P = 0.027). The overall mean CTC number was 2.0 (range 0-56.3). The mean CTC number in patients with diffuse metastases was significantly higher (3.7 [SEM ± 1.7, range 0-56.3]) than with limited lung metastases (0.1 [± 0.1; range 0-1]) or liver metastases (0.9 [± 0.3, range 0-7.0]) (P = 0.001). CRC tumors were consistently expressing EpCAM. CTC numbers did not correlate with serum CEA levels or other routine clinical parameters (P = N.S.). Patients with diffuse metastases had the poorest overall survival (P = 0.0042).
  
  
  CONCLUSIONS
  CRC patients with diffuse metastases have the highest number of CTCs, in contrast to limited metastases to the liver or lungs. Future studies should correlate CTCs with recurrence patterns in patients with resected CRC lung or liver metastases to investigate whether CTCs represent micrometastatic disease causing early relapses.
authors.affiliation: Division of Surgical Oncology; Hollings Cancer Center; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.affiliation: Laboratory of Translational Oncology and Experimental Cancer Therapeutics; Division of Hematology/Oncology; Department of Medicine; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kunkel
authors.affiliation: Department of Public Health Sciences; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Translational Oncology and Experimental Cancer Therapeutics; Division of Hematology/Oncology; Department of Medicine; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Dicker
authors.affiliation: Section of Surgical Oncology; Department of Surgery; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Gusani
authors.affiliation: Department of Pathology; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Radiology, Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Nabeel E
authors.initials: NE
authors.lastname: Sarwani
authors.affiliation: Division of Surgical Oncology; Hollings Cancer Center; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology; Hollings Cancer Center; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Kimchi
authors.affiliation: Division of Surgical Oncology; Hollings Cancer Center; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Staveley-O'Carroll
authors.affiliation: Laboratory of Translational Oncology and Experimental Cancer Therapeutics; Division of Hematology/Oncology; Department of Medicine; Penn State Hershey Cancer Institute; Pennsylvania State University; Hershey, PA USA.
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D055815:Young Adult
keywords: circulating tumor cells; colorectal cancer; metastasis