CA 19-9: not a magic marker for pancreatic cancer.

Serum carbohydrate antigen (CA) 19-9 is considered to be the most sensitive/specific marker for pancreatic cancer, although it has also been associated with biliary, hepatocellular, gastric, colonic and nongastrointestinal malignancies. (1) For pancreatic adenocarcinoma, CA 19-9 is reported to have a sensitivity of 70 to 90%, specificity of about 90%, a positive predictive value of 69%, and a negative predictive value of 90%. (2)

Sakahara et al (3) reported an elevated CA 19-9 level in 87% of pancreatic cancer patients, and serum levels correlated with tumor size in most patients. The absence of an elevation in serum CA 19-9 levels in 13% of pancreatic cancer patients has been attributed to the fact that approximately 5% of Caucasians lack the Lewis A antigen, which synthesizes CA 19-9. (4) Kim et al (5) have recently concluded that CA 19-9 measurement is not a useful screening test for pancreatic cancer in the asymptomatic population.

In this issue of the Journal, Lowe et al (6) report the case of a 66-year-old white male who presented with cholestatic jaundice and a 30 pound weight loss over the preceding 2 months. Apart from abnormal liver function tests (LFTs) suggestive of obstructive jaundice, CA 19-9 level was significantly elevated at 4,374 U/mL. Abdominal imaging, including an ultrasound, hepatobiliary scan and computed axial tomography (CAT) were unremarkable. Endoscopic retrograde cholangiopancreatography (ERCP) showed a possible filling defect in the common bile duct (CBD). Sphincterotomy and balloon sweep of the CBD was performed. Follow-up LFTs and CA 19-9 levels at one year were within normal limits. A repeat CAT scan of the abdomen at this time was suggestive of possible pancreas divisum.

Elevated CA 19-9 levels in the absence of malignancy have been previously reported. Obstructive jaundice is associated with elevated CA 19-9 levels. A strong correlation between serum levels of CA 19-9 and biochemical indicators of cholestasis, alkaline phosphatase and bilirubin, during acute liver failure, acute hepatitis and chronic liver disease of any etiology has been reported. (7) Elevated CA 19-9 levels seen in the above conditions and as seen in cholangitis and choledocholithiasis may be due to the increased production and/or release of the antigen from the inflamed epithelial cells. The elevated biliary tract pressures may result in an exaggerated leakage of CA 19-9 into the serum. A relief of the elevated pressures by way of improved biliary drainage and/or resolution of infection/inflammation results in a decline in the CA 19-9 levels. (8) Elevated CA 19-9 levels have also been reported in patients with rheumatologic conditions, including rheumatoid arthritis, systemic lupus erythematosus and scleroderma. (9)

While the cause of elevated CA 19-9 in the case described in this issue of the Journal is unclear, a cause of obstructive jaundice is likely. This case highlights the need to interpret elevated CA 19-9 levels with caution; clinicians need to be aware of the nonmalignant causes of elevated CA 19-9 levels and rule them out before initiating a workup for malignancy. Also, the use of CA 19-9 levels as a screening tool for pancreatic cancer should be discouraged.

References

1. Koprowski H, Steplewski Z, Mitchell K, et al. Colorectal carcinoma antigens detected by hybridoma antibodies. Somat Cell Mol Genet 1979; 5:957-971.

2. Duffy MJ. CA 19-9 as a marker for gastrointestinal cancers: a review. Ann Clin Biochem 1998;35:364-370.

3. Sakahara H, Endo K, Nakajima K, et al. Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma. Cancer 1986;57:1324-1326.

4. Albert MB, Steinberg WM, Henry JP. Elevated serum levels of tumor marker CA 19-9 in acute cholangitis. Dig Dis Sci 1988;33:1223-1225.

5. Kim J, Lee K, Lee J, et al. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol 2004;19:182-186.

6. Lowe D, Lee J, Schade R, et al. Patient with markedly elevated CA 19-9 not associated with malignancy. South Med J 2006;99:306-308.

7. Maestranzi S, Przemioslo R, Mitchell H, et al. The effect of benign and malignant liver disease on the tumour markers CA 19-9 and CEA. Ann Clin Biochem 1998;35:99-103.

8. Mann DV, Edwards R, Ho S, et al. Elevated tumour marker CA 19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol 2000;26:474-479.

9. Shimomura C, Eguchi K, Kawakami A, et al. Elevation of a tumor-associated antigen CA 19-9 in patients with rheumatic diseases. J Rheumatol 1989;16:1410-1415.

Sumanth R. Daram, MD

From the Department of Internal Medicine, Saint Joseph Regional Medical Center and Medical College of Wisconsin, Milwaukee, WI.

Reprint requests to Sumanth R Daram, MD, Clinical Assistant Professor of Medicine. Department of Internal Medicine, Saint Joseph Regional Medical Center, 5000 W Chambers, #PIMS, Milwaukee, WI 53210. Email: [e-mail]

Accepted December 21, 2005.