title: Part I. Telomerase levels in human metastatic brain tumors show four-fold logarithmic variability but no correlation with tumor type or interval to patient demise.
abstract: Telomerase expression has been found in the majority of human neoplasms at their primary sites and, in some tumor types, has been correlated with patient prognosis. In part one of this two-part study, we investigated whether telomerase was expressed ubiquitously in metastases to the brain and whether varying levels of expression existed or correlated with patient prognosis. A second aim of this study was to acquire data on brain metastases preliminary to the investigation of whether the telomerase assay could be used for the detection of tumor cells in cerebrospinal fluid (CSF). We investigated 35 brain metastases utilizing the sensitive telomeric repeat amplification protocol (TRAP) assay coupled with densitometric quantitation of telomerase levels on frozen, banked tissue specimens. Specimens metastatic to the brain analyzed in this study included melanoma, adenocarcinoma, hepatocellular carcinoma, germ cell neoplasm, squamous cell carcinoma, osteogenic sarcoma, and secondary lymphoma. Telomerase was found in 32 of 35 metastases. Quantitation of the telomerase products showed a fourfold logarithmic variation, following standardization of protein concentrations. Levels of telomerase expression showed no statistical correlation with either tumor subtype or interval from date of procedure to patient demise. Interestingly, in two patients with two metastatic samples each taken at discordant times, the telomerase levels were higher in the metastasis specimen taken closer to the time of demise. This suggests a possible increase in telomerase level within a given patient's neoplasm as the disease became more advanced, although too few cases were available to reach a firm conclusion in this regard. We conclude that most brain metastases express telomerase, albeit at widely varying levels, which are not clearly correlated with patient survival. These results influence the potential utility of telomerase analysis for the detection of small numbers of metastatic tumor cells in CSF, as addressed in the companion manuscript.
authors.affiliation: University of Colorado Health Sciences Center, Department of Pathology, Denver 80262, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.forename: A L
authors.initials: AL
authors.lastname: Shroyer
authors.forename: T L
authors.initials: TL
authors.lastname: Hashizumi
authors.forename: L C
authors.initials: LC
authors.lastname: Evans
authors.forename: N
authors.initials: N
authors.lastname: Markham
authors.forename: G
authors.initials: G
authors.lastname: Kindt
authors.forename: K R
authors.initials: KR
authors.lastname: Shroyer
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D019098:Telomerase / Q000378:metabolism*
chemical_list: D019098:Telomerase