1. Cancer Antigen 15-3 Alison Nolan DT204/2

2. What is Cancer?  Cancer is a disease which is characterized by uncontrolled proliferation of cells.  This proliferation occurs through mutations in short circuit growth pathways, evasion of growth inhibitory signals, evasion of immune response and the ability to replicate endlessly.  Similarly, cancer can become a disease of multiple sites, spreading from a primary tumour and invading other tissues in the body.  Over 100 different types of cancer have been classified (Pecorino L, 2012).

3. What is CA 15-13?  Cancer Antigen 15-3 is a glycoprotein which is produced as a polymorphic epithelial mucin (antigen) on the surface of carcinoma cells.  It is commonly associated with breast cancer as raised levels of Ca15-3 in serum can give an indication of breast cancer.  However it can also be associated with other diseases such as cancers of the liver and pancreas, PID and endometriosis.  Clinically, it can act as a maker for the spread of breast cancer or metastasis. Metastasis occurs when a primary tumour has spread to another area of the body.  Raised levels of Ca15-3 are usually only seen in the late stages of breast cancer or when metastasis has already occurred.

4. What is CA15-3 used for?  High concentrations of Ca15-3 are usually only seen in the late stages of breast cancer.  Although not used as a biomarker for the presence of cancer due to its late stage appearance its levels in serum can be used to monitor a patient’s response to treatment.  During radiation and chemotherapy, levels of Ca15-3 can be monitored using a simple serum assay.  Increased concentrations of Ca15-3 suggest progression of cancer and a decreased value suggests regression.

5. Methods to Measure Ca15-3  An Immunoassay based on both the antibodies 115 D8 and DF3 is carried out in a clinical setting: 1) The antibody 115 D8 acts as a catcher meaning it is placed in the well in a solid phase. 2) Patient serum containing the antigen is added and the monoclonal antibody 115 D8 can bind to the antigen’s epitope. 3) The antibody DF3 is enzyme-conjugated and is added to the assay, acting as the tracer. 4) The combination of both antibodies allows the correct binding of the antigen epitope and for levels of Ca15-3 to be detected in patient serum.

6. Assay Controls  As with any other scientific assay it is necessary to include controls.  To save time in a laboratory pre-prepared laboratory controls are bought used in this assay and are diluted by the technician accordingly. An example of this is the Abbott AxSYM System.  Two controls are used, one depicting the normal values that we expect to see in patients not suffering from disease and one which exhibits values above the threshold for normality.  In the Abbott system Ca15-3 levels are measured in Units/µl.  A normal reference value will usually be around 30 U/µl.

7. References  Panall P and Kotasek D, Cancer and Clinical Biochemistry, Eds McCreanor G, Marshall W, 1997,pp42,58  Pecorino L, Molecular Biology of Cancer, Oxford University Press, 3 rd Edition. 2012, pp197-200  From Clone to Clinic, Eds Daan J.A. Crommelin, H. Schellekens, softcover reprint, 1990, Chapter 1  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679379/ (accessed 10 th of February 2016) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679379/  http://www.cancer.ca/en/cancer-information/diagnosis-and-treatment/tests-and- procedures/cancer-antigen-15-3-ca-15-3/?region=on (accessed 10 th of February 2016) http://www.cancer.ca/en/cancer-information/diagnosis-and-treatment/tests-and- procedures/cancer-antigen-15-3-ca-15-3/?region=on  http://www.ilexmedical.com/files/PDF/CA15-3_AXS.pdf (accessed 10 th of February 2016) http://www.ilexmedical.com/files/PDF/CA15-3_AXS.pdf  http://link.springer.com/chapter/10.1007/978-94-011-3780-5_14#page-1 (accessed 10 th of February 2016) http://link.springer.com/chapter/10.1007/978-94-011-3780-5_14#page-1