Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines
Introduction
Biochemical markers for colorectal cancer (CRC) are potentially useful in screening for early disease, aiding diagnosis, determining prognosis, predicting likely response to specific therapies, surveillance of patients undergoing curative resection and monitoring the treatment of advanced disease. Although multiple markers have been described for CRC, confusion remains about how best to use these factors.
The European Group on Tumour Markers (EGTM) is an ad hoc group of scientists and physicians from universities, hospitals and the diagnostics industry with an interest in tumour markers [1]. The group was founded in 1997, one of its aims being the development of guidelines for the use of tumour markers. Adherence to these guidelines is of course voluntary since the ultimate decision regarding marker use must be made by the treating clinician. It is also important to note that the present guidelines are intended for routine clinical use and do not necessarily apply to clinical trials, which may have a different remit.
In 1999, the Gastrointestinal Focus Group of the EGTM published a review on the use of markers in colorectal, stomach, oesophageal, pancreatic and liver cancers [2]. The aim of this paper was to present guidelines for the clinical use of markers in CRC, focusing primarily on carcinoembryonic antigen (CEA), the most widely used marker for this malignancy.
Section snippets
Structure and function
CEA is a high molecular weight glycoprotein belonging to the immunoglobulin superfamily of molecules (for review, see Refs. 3, 4). The molecule consists of a series of Ig-like domains including a 108 amino acid variable or v region at the amino terminus, and 3 pairs of constant-2 (C-2)-like domains, each containing 178 amino acids. The carboxy-terminal contains a hydrophobic region that is modified to provide a glycosyl phosphatidylinositol link to the cell membrane.
CEA has been postulated to
Other serum markers
Although the oldest, CEA is still the best available serum marker for CRC. One of its major limitations in monitoring, however, is that 20–30% of patients with CRC fail to produce elevated serum levels, despite the presence of advanced disease. For the follow-up of these patients, other markers are therefore necessary. Markers that are of potential value for CRC patients not expressing high levels of CEA include CA 19-9, CA 242, CA 72-4, CA 50, TPA (tissue polypeptide antigen), TPS (tissue
Screening and early diagnosis
All the currently used markers for CRC have 2 main disadvantages, i.e., lack of sensitivity for early or premalignant disease and lack of specificity for malignancy. It is, however, now well established that multiple molecular alterations occur at the genome level, during the transition from normal mucosa to invasive carcinoma [53]. Genes undergoing mutation during this process might be expected to provide markers that are relatively specific for malignant or premalignant disease and also aid
Suggestions for future research
Using prospective randomised trials where possible, the following studies should be carried out:
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Establish whether serial levels of CEA enhance patient outcome, quality of life or cost of care,
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Investigate if elevated preoperative CEA levels can be used to select the aggressive Dukes’ B (node-negative) patients that could benefit from adjuvant chemotherapy.
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Establish the variations in serial CEA levels that optimally define tumour progression and regression,
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Using multivariate analysis, compare the
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