carcinoembryonic antigen (CEA)

Carcinoembryonic Antigen

1. Carcinoembryonic Antigen (CEA) was first discovered in 1965 by Gold and Freedman (Miyake et al. 1979). Gold and Freedman isolated the CEA from adult cancerous colon tissue and foetal intestines. CEA's however were absent from healthy adult colon (Duffy, 2001). It was first thought that CEA was an antigen specific to cancers originating in the colon (Miyake et al., 1979).

CEA is a glycoprotein with a size of around 200kDa and consisting of around 670 amino acids. Human CEA coding gene is part of an immunoglobulin superfamily located on chromosome 19, which includes ICAM-1 and antigens of the Major histocompatibility complex (Duffy, 2001). CEA's are situated in the human colon anchored through a hydrophobic region to epithelial cells called enterocytes. The glycoprotein extends outwards from the colon membrane. The exact role of CEA is still misunderstood, with research identifying CEA with a number of roles in the human body such as cell adhesion in binding to bacteria e.g. E. coli, protecting the gut from infection and possibly involved in cancer metastasis. Later research found that CEA was associated with healthy tissues, other cancers such as lung, liver, breast, bladder (Saied et al., 2007) and pancreas (Miyake et al,. 1979) and in diseases such as hepatitis, pancreatitis, colitis and cirrhosis. CEA is also associated with cigarette smokers.

CEA over the last thirty years has been used as a worldwide tumour marker and cancer treatment monitor for colon and rectal cancers. However there is still considerable debate whether detection of CEA's can be used as a tool in cancer screening due to the high incidents of false positive results. An extremely high level of CEA's in a patient would suggest however the presence of a cancer.

2. Carcinoembryonic Antigens can be detected by either using Immunoenzymatic colorimetric or radioimmunoassay (RIA) techniques.

Currently enzyme-linked immunosorbent assays (ELISA) are used to detect specific CEA's within a patient's serum sample. CEA's are detected using an antibody-antigen sandwich ELISA. The patient's serum sample is added to a microplate, which is coated with streptavidin. The CEA in the sample will bind to the streptavidin and be immobilized on the well wall. Horseradish peroxidase (HRP) enzyme conjugated antibody is then added to the well containing the sample. The conjugated antibody binds to surface epitopes on the CEA. The microplate is washed with deionised water to remove any unbound molecules. To see if the antibodies have bound to the CEA a substrate called tetramethyl-benzidine (TMB) is added to the sample wells. The substrate binds to the enzyme conjugated to the antibody. A stop solution such as sulphuric acid is added, which turns the colour of the wells yellow or blue. The absorbance of the wells at 450nm is measured using a spectrophotometer. The absorbance values of the sample can be then compared against a standard curve. New methods have been investigated such as a polymerase chain reaction of mRNA from tumour-specific antigens L6 (Schiedeck et al., 2001). There is however problems associated with the ELISA technique due to CEA's being produced from smoking and benign tumours leading to a false positive result.

3. Carcinoembryonic Antigens are the main tumour markers for colon and rectal cancers. CEA's are associated with a number of cancers and non-cancerous diseases. The desired levels of CEA's in a healthy human adult are around 2-3 ng/ml (Duffy, 2001). Levels above this threshold are not normal and require investigation. Adult smokers however have an average CEA reading of <5 ng/ml. This must be taken into account when making a diagnosis. CEA's are also used to monitor the progress of a cancer treatment such as chemotherapy or in a postoperative patient. CEA's are rarely used to screen the early stages of a colon or rectal cancer due to low levels of CEA's in the blood (Duffy, 2001).

4. The graph shows the levels of CEA (ng/ml) from a patient over a period of 18 months. The patient in the beginning has a high CEA value of 250-300 ng/ml this suggests the patient has developed a cancer probably colorectal. The patient however may also have had cancer in the past and was treated but the cancer has returned.

The patient is undergoing or has undergone treatment for a colorectal cancer. The treatment may have been chemotherapy or surgery to remove part of the bowel that contains the cancer. Following the cancer treatment the CEA values usually decrease after about six weeks to a normal level, as shown in the graph. This suggests the patient is responding well to treatment.

The patient is monitored over a period of months to see the effect of the treatment. The patients CEA values over this period fluctuate but remain at a normal level. After a year the patients CEA values begin to increase again from 6 ng/ml to around 70 ng/ml. This suggests that the chemotherapy is not responding to the cancer or there are remaining pockets of cancerous bowel, which haven't been removed by surgery. Chemotherapy may also increase the levels of CEA as dead tumour cells release CEA's

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