Part II. Telomerase expression in cerebrospinal fluid specimens as an adjunct to cytologic diagnosis

The diagnosis of meningeal carcinomatosis hinges on the cytologic examinati on of cerebrospinal fluid (CSF), which has a known low sensitivity for the identification of malignant cells. Often only 'suspicious' or 'atypical' di agnoses can be rendered, and specimens are commonly unsatisfactory for eval uation due to poor morphologic preservation. Telomerase is widely expressed in most brain metastases, medulloblastomas, lymphomas, oligodendrogliomas, and is expressed focally in glioblastomas. Little is known about the level of telomerase expression in these tumors, except for brain metastases, whe re a four-fold variation in telomerase levels exists. In our laboratory, as few as ten carcinoma cells can be detected by a sensitive polymerase chain reaction-based assay, the telomeric repeat amplification protocol (TRAP), for telomerase, but it was unclear whether varying levels of telomerase exp ressed by different types of metastases would influence detection. Using th e TRAP protocol, we studied 281 CSF samples from a wide variety of patients with neurologic and non-neurologic conditions for telomerase expression. A n adjusted specificity of 90% and a sensitivity of 64% were achieved for de tection of malignant cells in CSF by telomerase expression. The TRAP assay for telomerase detection may serve as an adjunct to the traditional examina tion of CSF. Neither previously documented four-fold variation in the level s of telomerase expression in brain metastases, high CSF protein levels nor high white blood cell counts precluded detection of malignant cells in CSF . (C) 1998 Published by Elsevier Science B.V. All rights reserved.