Part II. Telomerase expression in cerebrospinal fluid specimens as an adjunct to cytologic diagnosis.
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.
Kleinschmidt-DeMasters
B K
BK
University of Colorado Health Sciences Center, Department of Pathology, Denver 80262, USA.
Evans
L C
LC
Bitter
M A
MA
Shroyer
A L
AL
Shroyer
K R
KR
D000328:Adult; D000368:Aged; D003581:Cytodiagnosis / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000201:enzymology; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000134:cerebrospinal fluid*
D019098:Telomerase