Sensitive quantitation of carcinoembryonic antigen in cerebrospinal fluid and its barrier-dependent differentiation

Abstract

Modification of an enzyme immunoassay using beads as solid phase allows the detection of 3 pg/ml carcinoembryonic antigen (CEA). The beads are shown to be advantageous for the extraction of proteins in highly diluted antigen solutions thus replacing a need for concentration of the sample. The mean concentration of CEA in pooled cerebrospinal fluid (CSF) from 120 control persons was shown to be 2.7 pg/ml. The mean of the CSF/serum concentration quotients of CEA was 0.0015 for normal blood CSF barrier function with a corresponding mean albumin CSF/serum quotient of 0.0048. From the ratio of these two quotients ( Q CEA/ Q A = 0.31) and the corresponding biological variation we constructed the normal range of an evaluation graph. In the range of a blood CSF barrier dysfunction, the discrimination line between values with or without a local CEA synthesis in brain was determined to be Q CEA = 0.7 Q A. Twenty-five out of 383 control persons and 29 out of 45 patients with a tumor metastasis had evaluable quotients. The evaluation graph had a high significance with respect to the identification of tumor metastasis: from a group of patients with a confirmed leptomeningeal metastasis 13 out of 13 and from a group of patients with intraparenchymatous tumor metastasis 10 out of 16 could be identified by CSF analysis. The CEA CSF/serum concentration quotient fits well in the concept of a molecular size-dependent filter function of the blood CSF barrier.