Characterization of serum and urinary chromogranin A by size exclusion chromatography: Impact on calibrator selection and urinary assay

Serum chromogranin A (CSA) is a useful marker for neuroendocrine tumors and is detectable in carcinomas at advanced stages. Elevated serum CgA is also an indicator of poor prognosis in prostate cancer and is useful for predic ting the failure of hormonal therapy for prostate cancer patients. We found that CgA molecules with three different sizes could be detected in normal human serum. However, only the largest CgA molecule appears in patients wit h liver disease. Serum taken from cancer patients is composed predominantly of the middle-sized molecule, whereas the smallest CgA molecule was elevat ed in serum drawn from renal patients. Moreover, only the smallest CgA mole cule was found in urine. We believe that the largest CgA molecule is metabo lized by the liver, whereas the smallest CgA molecule is removed from the b lood circulation via the kidney. Because the medium-sized CgA is the domina nt molecule in both the cell medium of the tumor cell line SK-N-AS and sera from patients with malignant diseases, CgA from the cell medium was select ed as the calibrator for the CgA ELISA assay. Our findings also suggest tha t it would not be possible to measure the urinary CgA to reflect the serum CgA concentration in order to detect pheochromocytoma among patients with h ypertension. (C) 2001 Wiley-Liss, Inc.