Sunday, December 2, 2012

Carbohydrate antigen 19-9 – Pancreatic Cancer Tumor Market

Although there are no screening tests currently available to screen the general population, investigators in the USA are working on developing the relevant tests for the further early disease detection. It is hoped that these new tests may prove effective, particularly when applied to select groups of patients known to have an increased risk of developing pancreatic cancer such as individuals with a strong family history.

Many tumor markers have been identified; some of them are available for use while others are still being studied.

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CA19-9 is the most useful available tumor marker for following the progression of the disease but is only 80% accurate in identifying patients with pancreatic cancer. The value of CA19-9 in therapy monitoring is established; in most follow-up studies the sensitivity reached 100% in detection of recurrent disease. Due to the inability of CA19-9 to identify early potentially curable disease, several other markers have been studied including SPAN-1, CA 242, CA-50, CEA, DUPAN-2, elastase-1, tissue polypeptide antigen and tissue polypeptide specific antigen. However, these markers have not performed nearly as well as the CA19-9.

The major useful tumor marker for pancreatic carcinoma is the carbohydrate antigen 19-9 (CA 19-9). It is a murine monoclonal antibody originally made against colorectal cancer cells. The CA 19-9 antigen is a sialylated oligosaccharide that is most commonly found on circulating mucins in cancer patients. It is also normally present within the cells of the biliary tract and can be elevated in acute or chronic biliary disease. In healthy people 5-10% lack the enzyme to produce CA 19-9.

The reference range of CA 19-9 is less than 33-37 U/mL. Of patients with pancreatic carcinoma, 75-85% have elevated CA 19-9 levels. In the absence of biliary obstruction or benign pancreatic disease, a CA 19-9 value greater than 100 U/mL is highly specific for malignancy, usually pancreatic.

Evaluation of CA 19-9 levels has been used as an adjunct to imaging studies for helping determine the resectability potential of pancreatic carcinoma. Fewer than 4% of patients with a CA 19-9 level of more than 300 U/mL have been found to have resectable tumors.

Unfortunately, CA 19-9 is least sensitive for small early-stage pancreatic carcinomas and thus has not proven to be effective for the early detection of pancreatic cancer or as a screening tool.

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An elevated CA 19-9 level is found in 0.2% of an asymptomatic population older than 40 years. Of these elevations, 80% are false-positive results. If only symptomatic patients are studied, 4.3% have elevated CA 19-9 levels. Two thirds of these results are false positive. To date, no standardized role has been found for CA 19- 9 measurements in pancreatic carcinoma, and the usefulness of this practice must still be classified as only a supplement to other diagnostic modalities.

An ideal pancreatic cancer screening test should be a safe, inexpensive, highly accurate test that reliably diagnoses pancreas cancer at a stage when it is not causing symptoms in the patient. This would provide an opportunity to take appropriate and effective action to treat and potentially cure the disease. Currently, we cannot offer a screening test for pancreas cancer that could meet these demands. However, the potential for screening this disease is considerably improved compared to just a few years ago.

First of all, we know more about which individuals have a genetic predisposition for developing this disease. Prior to the 1990’s, it was not widely appreciated how often pancreatic cancer is an inherited disease. Now we know that individuals with abnormalities in certain genes, such as BRCA2, p16, HNPCC, and individuals with histories of familial pancreatitis and Peutz-Jeghers syndrome are all predisposed to pancreatic cancer. These are important discoveries. However, individuals who inherit damage to one of these genes still represent only a modest proportion of all those individuals at risk of developing pancreatic cancer.

Genetic testing for mutations in CDKN2 is now available clinically, however, technically not used for screening. Four healthy carriers of CDKN2mutations, all children of parents who died of pancreatic carcinoma, are currently being followed in the USA. Regular endoscopic ultrasound of the pancreas is ongoing and pancreatic juice is being collected for analysis of telomerase activity, Kras mutations, CA19-9, and other candidate biomarkers. K-ras mutations, detected by PCR, was found to contribute to the clinical decision process when the cancer is clinically suspected.

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Secondly, we now know much more about the changes in the DNA and other molecules in the pancreas cells that give rise to pancreatic cancer. Most of these changes are not inherited and occur as the result of factors such as smoking, diet, and age. Importantly, pancreatic cancer researchers are characterizing these specific changes in DNA and other molecules. It is hoped that over the next few years, specific and extremely sensitive screening tests will be developed. Such a screening test will be able to detect pancreatic cancer at an early stage when it still cannot be visualized using state of- the-art diagnostic imaging techniques. Once such a screening panel is in place, it can be offered to individuals who, from their family history, know that they are at particular risk of developing this disease.

Currently many new screening tools are being investigated. Carcinoembryonic antigen (CEA) is a high molecular weight glycoprotein found normally in fetal tissues. It has commonly been used as a tumor marker in other gastrointestinal malignancies. However, it has minimal utility in pancreatic carcinoma. The reference range is less than or equal to 2.5 mg/mL. Only 40-45% of patients with pancreatic carcinoma have elevations in CEA levels. Multiple other benign and malignant conditions can lead to elevated CEA levels; thus, CEA is not a sensitive or specific marker for pancreatic cancer.

Pure pancreatic juice (PPJ) cytology and tumor marker (CEA) determination has been evaluated for the diagnosis of early pancreatic cancer. The authors conclude that combined cytology and CEA determination in PPJ, with a diagnostic accuracy of 93%, could be useful for the diagnosis of pancreatic cancer even in early stages.

Other tumor markers which are currently being studied for early diagnosis of pancreatic cancer include CA 242 and CA 50. Studies comparing CA-242 levels in benign and malignant pancreatic tumors found no difference and concluded that this marker cannot compare with CA 19-9. In other studies the two tumor markers had almost a similar prognostic value.

Tissue polypeptide specific antigens (TPS) has been studied as a marker for differentiation between chronic pancreatitis and pancreatic cancer. Almost complete discrimination of the two was attained; the researchers concluded that TPS is more useful than CA 19-9 in the differential diagnosis of the two conditions.

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