Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the cyclooxygenase-2 locus and decreased patient survival in advanced colorectal carcinomas.
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.
Knösel
Thomas
T
Institute of Pathology, Charité Campus Mitte, Berlin, Germany.
Yu
Yongwei
Y
Stein
Ulrike
U
Schwabe
Holger
H
Schlüns
Karsten
K
Schlag
Peter Michael
PM
Dietel
Manfred
M
Petersen
Iver
I
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
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases