title: Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the cyclooxygenase-2 locus and decreased patient survival in advanced colorectal carcinomas.
abstract: OBJECTIVE
  Overexpression of cyclooxygenase-2 is observed in a variety of malignancies including colorectal cancer. However, to date, cyclooxygenase-2 expression by advanced human colorectal cancers and their metastases has been poorly characterized. This study was designed to evaluate the rate of cyclooxygenase-2 overexpression in our tumor collection and to clarify its correlation with the chromosomal status at the cyclooxygenase-2 locus in colorectal cancer.
  
  
  METHODS
  Seventy-four specimens were analyzed immunohistochemically using a monoclonal cyclooxygenase-2 antibody. The staining was scored semiquantitatively as: -, negative; +, weak; ++, moderate; and +++, strong positive. Of these, 45 specimens were analyzed using comparative genomic hybridization and immunohistochemistry. We correlated the cyclooxygenase-2 overexpression with the chromosomal gain of 1q25.2-q25.3 and patients survival and compared primary colorectal cancers and their paired metastases at the DNA and protein level.
  
  
  RESULTS
  Overexpression was observed in 58 percent of the cases (score > or = ++). Chromosomal gains at the cyclooxygenase-2 locus were clearly correlated with overexpression of the gene (P=0.009). Furthermore, the comparison of paired tumor samples showed additional overrepresentation in the metastases at the cyclooxygenase-2 locus, which could be confirmed by immunohistochemistry. Kaplan-Meier analysis showed that overexpression of cyclooxygenase-2 was significantly associated with poor survival and thus could serve as a prognostic marker.
  
  
  CONCLUSIONS
  We conclude that cyclooxygenase-2 is related with tumor progression and metastasis in colorectal cancer, which can be observed on protein level, and reflects chromosomal gain at the locus at 1q25.2-q25.3.
authors.affiliation: Institute of Pathology, Charité Campus Mitte, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stein
authors.forename: Holger
authors.initials: H
authors.lastname: Schwabe
authors.forename: Karsten
authors.initials: K
authors.lastname: Schlüns
authors.forename: Peter Michael
authors.initials: PM
authors.lastname: Schlag
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D051546:Cyclooxygenase 2; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics*; D008565:Membrane Proteins; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases