Premium
Implications of low COX‐2 expression in colorectal neoplasms with defective DNA mismatch repair
Author(s) -
Karnes William E.
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(2000)77:34+<23::aid-jcb6>3.0.co;2-8
Subject(s) - microsatellite instability , loss of heterozygosity , dna mismatch repair , cancer research , colorectal cancer , biology , dna repair , colorectal adenoma , adenoma , chromosome instability , pathology , cancer , dna , genetics , medicine , gene , microsatellite , chromosome , allele
Most colorectal adenomas and carcinomas arise in the setting of chromosomal instability and progressive loss of heterozygosity. Approximately 15–20% of colorectal neoplasms arise through a distinct genetic pathway characterized by microsatellite instability (MSI) and frequent loss of expression of one of the DNA mismatch repair enzymes, most often hMLH1 or hMSH2. These distinct genetic pathways are reflected by differences in tumor histopathology, distribution in the colon, prognosis, and dwell time required for progression from adenoma to carcinoma. The molecular and clinical distinctions between these tumors suggest that they are biologically distinct and may respond differently to therapeutic and chemopreventive agents. Recently, we showed that expression of a putative chemopreventive target, COX‐2, is significantly reduced in colorectal cancers with defective mismatch repair as assessed by MSI and absent staining for hMLH1 and/or hMSH2. The mechanisms responsible for low COX‐2 expression in tumors with MSI remain unknown, but they may be linked to molecular events giving rise to MSI tumors. Although the clinical implications of these observations are unknown, the presence of MSI should be considered an important variable when assessing the efficacy of COX‐2 inhibitors in chemoprevention trials. J. Cell. Biochem. Suppl. 34:23–27, 2000. © 2000 Wiley‐Liss, Inc.