Journal of the Neurological Sciences 161 (1998) 124–134 Part II. Telomerase expression in cerebrospinal fluid specimens as an 1 adjunct to cytologic diagnosis a ,b , a a ,b c * B.K. Kleinschmidt-DeMasters , Lynnette C. Evans , Mitchell A. Bitter , A. Laurie Shroyer , a Kenneth R. Shroyer a University of Colorado Health Sciences Center, Department of Pathology, 4200 East Ninth Avenue, Denver, CO 80262, USA b University of Colorado Health Sciences Center, Department of Neurology, 4200 East Ninth Avenue, Denver, CO 80262, USA c Department of Cardiac Research, Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA Received 18 March 1998; received in revised form 25 June 1998; accepted 26 June 1998 Abstract The diagnosis of meningeal carcinomatosis hinges on the cytologic examination of cerebrospinal fluid (CSF), which has a known low sensitivity for the identification of malignant cells. Often only ‘suspicious’ or ‘atypical’ diagnoses can be rendered, and specimens are commonly unsatisfactory for evaluation 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, where 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 expressed by different types of metastases would influence detection. Using the TRAP protocol, we studied 281 CSF samples from a wide variety of patients with neurologic and non-neurologic conditions for telomerase expression. An adjusted specificity of 90% and a sensitivity of 64% were achieved for detection of malignant cells in CSF by telomerase expression. The TRAP assay for telomerase detection may serve as an adjunct to the traditional examination of CSF. Neither previously documented four-fold variation in the levels of telomerase expression in brain metastases, high CSF protein levels nor high white blood cell counts precluded detection of malignant cells in CSF.  1998 Published by Elsevier Science B.V. All rights reserved. Keywords: Cerebrospinal fluid; Cytology; Meningeal carcinomatosis; Metastases; Telomerase; Central nervous system; Brain; Prognosis 1. Introduction to be expressed at low levels in proliferative tissues, including germ cells, endometrium, basal keratinocytes and Telomerase is a ribonucleoprotein enzyme complex that lymphoid cells [22,30,31]. High telomerase expression, by synthesizes G-rich, six base pair sequences onto the ends contrast, is characteristic of immortalized cells and is of chromosomes, known as telomeres [1]. Telomeric found in the vast majority of all cancers [23]. While the reduction signals the cessation of cellular division and may grade and stage at which telomerase is expressed differs serve as a biological clock to regulate the lifespan of the for each given tumor type and site, high telomerase levels cell [15,22,30]. Telomerase is down-regulated in cells as are virtually always found in late-stage malignancies they undergo senescence or differentiation, but continues [4,5,7,17,18,21,23,33]. This nearly ubiquitous expression of telomerase in a * Corresponding author. Tel.: 1303-315-7298; fax: 1303-315-4792. wide variety of human neoplasms has prompted a plethora 1 Presented in abstract form at the 74th annual meeting of the American of reports addressing telomerase as a universal cancer Association of Neuropathologists, Minneapolis, MN, USA, on June 19 marker or therapeutic target [4,15,16,28,29,31,32,35, 1998, where it was the recipient of the Rubinstein award for the best paper in Neuro-oncology for 1998. 37,39]. Most studies have concentrated on analyzing tissue 0022-510X / 98 / $ – see front matter  1998 Published by Elsevier Science B.V. All rights reserved. PII: S0022-510X(98)00254-8