title: Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer.
abstract: BACKGROUND
  Cdc7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms and cancer progression. Recently, it has been suggested as a target for anti-cancer therapy.
  
  
  METHODS
  To determine the relationship of Cdc7 protein expression with tumor phenotype, molecular features and prognosis, 1800 colorectal carcinomas were analyzed by immunohistochemistry on a tissue microarray.
  
  
  RESULTS
  Cdc7 expression was considered negative in 33.6%, weak in 57.2% and strong in 9.2% of 1711 interpretable CRCs. Loss of Cdc7 expression was significantly associated with high tumor stage (p < 0.0001) and high tumor grade (p = 0.0077), but was unrelated to the nodal status (p = 0.5957). Moreover, a link between Cdc7 expression and the tubular histological tumor type was seen (p < 0.0001). p53 and Cdc7 expression were significantly linked to each other (p = 0.0013). In a multivariate survival analysis, strong Cdc7 expression of CRC was an independent marker of improved patient survival (p = 0.0031).
  
  
  CONCLUSIONS
  Our data show that Cdc7 is highly expressed in CRC and a potential therapeutic target in a subset of cancers with high p53 expression. Moreover, our findings strongly argue for a clinical utility of Cdc7 immunostaining as an independent prognostic biomarker in colorectal cancer enabling to select patients for adjuvant treatment.
authors.affiliation: Department of Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. n.melling@uke.de.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Melling
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. johannamuth@web.de.
authors.forename: Johanna
authors.initials: J
authors.lastname: Muth
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. r.simon@uke.de.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. c.bokemeyer@uke.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland. lterracciano@uhbs.ch.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. g.sauter@uke.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. izbicki@uke.de.
authors.forename: Jakob Robert
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. a.marx@uke.de.
authors.forename: Andreas Holger
authors.initials: AH
authors.lastname: Marx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases