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COX-2 may promote tumorigenesis by its ability to upregulate bcl-2 and thus inhibit apoptosis; in addition, overexpression of COX-2 may increase cell proliferation and angiogenesis, both of which contribute to an aggressive tumor phenotype.
A plethora of recent studies have shown overexpression of COX-2 in a variety of human malignancies, both gastrointestinal (colon, esophagus, stomach, pancreas), as well as outside the gastrointestinal tract (lung, breast,bladder, and cervix). Increased COX-2 levels have been shown to correlate with higher stage, larger tumor size, presence of lymphatic metastasis, risk of recurrence, and, most importantly, significantly poorer survival in colorectal cancers. These studies are now being extended to other tumor types, but the data on prognostic implications of COX-2 upregulation in most tumors besides colorectal neoplasms is still rudimentary.
Immunohistochemical detection of COX-2 levels in tissues offers a convenient and rapid approach for evaluating protein levels in tissues; this has the added advantage of being applicable to routine formalin-fixed archival material, and can be used for both prospective as well as retrospective analyses. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for COX-2 finally reflected in a histoscore on each evaluation. COX-2 comes as part of the standard colorectal panel, but can also be ordered individually.The test can be ordered if COX-2 inhibitors are being considered in the therapeutic regimen of various malignancies such as colorectal, ovarian, or breast. In addition, this laboratory offers COX-1 immunohistochemical analysis on clinical and research samples, although this is not currently included in any of the preformed panels. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Fosslien E. Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30:3, 2000
2. Katja C et al. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 59:198; 1999
3. Okami J et al. Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin Cancer Res 5:2018; 1999
4. Sano H et al. Expression of cycloxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785; 1995
5. Sheehan KM et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282:1254; 1999
6. Tomozawa S et al. Cyclooxygenase-2 overexpression correlates with tumor recurrence, especially hematogenous metastasis, of colorectal cancer. Br J Cancer 83:324; 2000
7. Whittle BJR. COX-1 and COX-2 products in the gut: therapeutic impact of COX-2 inhibitors. Gut 47:320; 2000
8. Wolff H et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58:4997; 1998
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