Tissue Polypeptide Antigen Activity in Cerebrospinal Fluid: A Marker of Central Nervous System Metastases of Breast Cancer

Abstract

Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition.