Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the cyclooxygenase-2 locus and decreased patient survival in advanced colorectal carcinomas

Item Type:	Article
Title:	Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the cyclooxygenase-2 locus and decreased patient survival in advanced colorectal carcinomas
Creators Name:	Knosel, T. and Yu, Y.W. and Stein, U. and Schwabe, H. and Schluns, K. and Schlag, P.M. and Dietel, M. and Petersen, I.
Abstract:	PURPOSE: 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 [greater than over equal to] ++). 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.
Keywords:	Chromosome 1, Comparative Genomic Hybridization, Tissue Microarray, Metastasis
Source:	Diseases of the Colon & Rectum
ISSN:	0012-3706
Volume:	47
Number:	1
Page Range:	70-77
Date:	January 2004
Official Publication:	https://doi.org/10.1007/s10350-003-0008-7
PubMed:	View item in PubMed

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