title: Aneuploidy and elevated CEA indicate an increased risk for metachronous metastasis in colorectal cancer.
abstract: OBJECTIVE
  Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear.
  
  
  METHODS
  Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM-). In addition, an enlarged collective (n = 217; n TM+ = 85, n TM- = 132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry.
  
  
  RESULTS
  The matched-pair collective showed aneuploidy in 71.1 % (TM-) and 85.0 % (TM+; p = 0.076), and elevated CEA in 24.5 % (TM-) and 52.2 % [TM+; odds ratio (OR), 3.414; p = 0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM-) and 83.5 % (TM+; OR 2.050, p = 0.038), and elevated CEA in 28.6 % (TM-) and 48.9 % (TM+; OR 2.391, p = 0.020). Elevated CEA and aneuploidy did not show any association (p = 0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p = 0.019), both elevated CEA level (OR 2.633, p = 0.015) and aneuploidy (OR 1.929, p = 0.058) were independent predictive markers for metachronous metastasis.
  
  
  CONCLUSIONS
  Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.
authors.affiliation: Laboratory of Surgical Research, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Laubert
authors.forename: Verena
authors.initials: V
authors.lastname: Bente
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.forename: Helena
authors.initials: H
authors.lastname: Voulgaris
authors.forename: Martina
authors.initials: M
authors.lastname: Oberländer
authors.forename: Katharina
authors.initials: K
authors.lastname: Schillo
authors.forename: Markus
authors.initials: M
authors.lastname: Kleemann
authors.forename: Conny
authors.initials: C
authors.lastname: Bürk
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D003710:Demography; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016015:Logistic Models; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D002272:Carcinoembryonic Antigen