1. Introduction and overview of CA19-9 CA19-9 is a tumour associated antigen found in the blood serum. CA 19-9 is also known as the Sialylated Lewis-antigen or carbohydrate antigen 19-9. The CA19-9 antigen is present in epithelial tissues of the pancreas, biliary duct cells, stomach, gall bladder, colon, salivary glands, and prostate. Pancreatic juice and seminal fluid also contain CA 19-9. (Halme, 2009) The sialylated Lewis A blood group antigen or CA19-9 is identified by an immunoassay. The Lewis antigen A- B- blood group which accounts for approximately 5% of the population do not produce the CA 19-9 antigen.

2. What disease is CA 19-9 related to? Elevated levels of CA 19-9 can be seen in benign conditions, such as the following: Biliary tract obstruction, cholangitis, inflammatory bowel disease, pancreatitis, liver cirrhosis, cystic fibrosis and thyroid disease. Elevated levels of CA 19-9 can be seen in the following malignant conditions: Bile duct cancers, Colorectal cancers, Gastric cancers, Ovarian cancers, Hepatocellular cancers and Esophageal cancers. (Harada, n.d.) The normal range of CA 19-9 in the blood of a healthy individual is 0-37 U/ml however, elevated levels of CA 19-9 can be seen in healthy individuals who are not suffering from a disease. (Locker, 2006)

3. The role of CA 19-9 in disease Ca19-9 levels are monitored in the blood serum of people suffering from pancreatic or colon cancer in order to determine the progression of the cancer and how the cancer is responding to treatment. Ca 19-9 levels can also be used to show a reoccurrence of cancer. CA 19-9 levels are not specific enough or sensitive enough to develop a cancer prognosis. If CA19-9 levels are initially elevated in patients with pancreatic cancer the levels can be monitored on an ongoing basis during the treatment to detect a reoccurrence. In the case of a suspected bile duct obstruction CA19-9 levels can be elevated, however these levels will decrease significantly once the blockage has been cleared. (Magnani, 2014)

4. The role of CA 19-9 in pancreatic cancer According to the National Cancer Registry Ireland almost 500 Irish people a year are diagnosed with pancreatic cancer, survival rates are very low, only 3% will survive after five years of diagnosis. The majority of patients that present with pancreatic cancer are at the advanced stages of the disease when the chances of curative treatment is significantly reduced. (O'Driscol, 2014). These findings clearly illustrate that pancreatic cancer is a very malignant disease and therefore early prognosis is essential. CA 19-9 is one of the many tumour markers proposed in order to develop a prognosis, monitor the cancer response to treatment and to detect a reoccurrence. A cancer prognosis should not be solely based on CA19-9 levels because they may fluctuate and not be an accurate representation of the pancreatic cancer.

5. Clinical studies on the use of CA 19-9 as a screening tool Kim et al carried out a study on the CA 19-9 serum levels on 70,940 asymptomatic individuals and only identified four patients with pancreatic cancer among the 1,063 with elevated CA19-9 serum levels. This study portrayed that CA19-9 can produce a weak positive predictive value of 0.9%, although the sensitivity and specificity were 100% and 98.5% respectively. Satake et al. analysed CA 19-9 serum levels in 8,706 individuals with symptoms suspicious for pancreatic cancer and 12,840 asymptomatic individuals. Among the 8,706 patients who presented with symptoms indicative of pancreatic cancer, 198 patients had raised CA19-9 serum levels, eight of these patients were found to have pancreatic cancer. (O'Driscol, 2014)

6. Clinical studies on the use of CA 19-9 as a screening tool These studies suggest that CA 19-9 serum levels produce poor predictive values, sub optimal sensitivity, and a low prevalence of pancreatic cancer in the population. Therefore, routine CA19-9 serum levels have little use as a screening tool in asymptomatic pancreatitis.

7. Commercial tests/systems Biocare Medical CA19-9 Concentrated and Prediluted Monoclonal Antibody DAKO – an Agilent technologies company Monoclonal Mouse Anti- Human CA 19-9 Clone 1116-NS-19-9 ELISA Kit for Carbohydrate Antigen 19-9 (CA19-9) SEA156Hu from USCN CA-19-9 AccuBind ELISA Kits are available from Monobind Inc No home kits are available.

8. Detection method We detect the CA 19-9 in tissues and cells by preforming a multi-step immunohistochemical process. The initial step involved in the assay is the binding of the primary antibody to its specific epitope. After labelling the antigen with a primary antibody, a secondary antibody is added to bind to the primary antibody. An enzyme label is then added to bind to the secondary antibody; the presence of a bound antibody can be detected by a colorimetric reaction. (Microwells, 2009)

9. CA 19-9 immunoassay controls Quality control: Each laboratory preforming the CA19-9 immunoassay should assay controls at low, normal and high range for monitoring assay performance. Quality control charts should be maintained to follow the performance of the supplied reagents. A normal level is less than 37 U/mL, which corresponds to a sensitivity of 81%, and a specificity of 90%. Positive predictive value :72% Negative Predictive Value of 96% (Microwells, 2009)

10. Reference list 1.Halme, L., 2009. Carbohydrate 19-9 antigen as a marker of non-malignant hepatocytic ductular transformation in patients with acute liver failure.. Gastroenterol, 5(34), pp. 426-31. 2.Harada, T., n.d. Usefulness of CA19.9 versus CA125 for the diagnosis of pancreatic cancer. Surgical Oncology. 3.Locker, G., 2006. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. Ann Oncology, 5(374), p. 145–9. 4.Magnani, J., 2014. The discovery, biology, and drug development of sialyl Lea and sialyl Lex. Archives of Biochemistry and Biophysics, 2(426), p. 122–31. 5.O'Driscol, D., 2014. Pancreatic Cancer Aetiology & Management - National Cancer Registry Ireland. [Online] Available at: http://www.ncri.ie/research/projects/pancam-pancreatic- cancer-aetiology-management. [Accessed 16 February 2016].http://www.ncri.ie/research/projects/pancam-pancreatic- cancer-aetiology-management 6.Pines, E., 2014. Unusually high CA19.9 in chronic pancreatitis. Gastroenteroology clinical biology, 3(54), pp. 134-137. 7.Microwells, A. C., 2009. CA19-9 Test System, California: Monodbind Inc.