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Letters |
1
Dept. of Pathol. and Lab. Med., Mount Sinai Hosp., 600 University Ave., Toronto, ON M5G 1X5, Canada,
2
Dept. of Neurol., Ottawa General Hosp., Ottawa, ON K1H 8L6, Canada,
3
Dept. of Clin. Biochem., Univ. of Toronto, Toronto, ON M5G 1L5, Canada
a Address correspondence to this author at Mt. Sinai Hospital.
To the Editor:
Improved, highly sensitive methods for measuring
prostate-specific antigen (PSA) (1) have shown that PSA is
present in many nonprostatic tissues and fluids (2).
Briefly, studies indicate that PSA production in both physiological and
pathological circumstances is not prostate- or sex-specific
(3)(4)(5), but rather a steroid hormone-mediated response
(6). PSA exists primarily in two immunoreactive forms: a
~33-kDa monomer (F-PSA) and a ~100-kDa complex with the protease
inhibitor
1-antichymotrypsin (PSA-ACT). In studies
involving ultrasensitive methodologies (detection limit of 1 ng/L PSA),
>50% of the sera from women have detectable PSA concentrations
(2)(7). Data indicate that the immunoreactive
PSA in sera from women without breast cancer is complexed with ACT,
whereas F-PSA predominates in sera from breast cancer patients
(8). In this letter we report for the first time PSA
presence in cerebrospinal fluid (CSF).
Ultrasensitive immunofluorometric PSA determinations in 299 CSFs from
subjects with various neurological disorders indicated a positive
result (>11 ng/L PSA) in 21 cases (7%). The age distribution of the
subjects in this study was 379 years, with a mean of 42, SD of 13.60,
and a median of 40 years. From the 20 PSA-positive cases for whom sex
and age were known, 13 (65%) were in the highest age quartile (>49
years old), indicating that PSA positivity depended on patient age
(
2 = 6.789, df = 1, P
<0.010). Eleven were of male origin, indicating no sex difference in
positivity. The PSA concentrations in positive CSFs from men were not
statistically different from those from women (P =
0.111 for MannWhitney test). The following observations are also
noteworthy: 6 of 129 (5%) with multiple sclerosis, 3 of 4 (75%) with
cerebral vasculitis, 2 of 3 (67%) with myelopathy, and 2 of 6 (33%)
with AIDS/HIV-associated neuropathic cases were positive for PSA. The
third highest PSA concentration found in CSF from this study (132 ng/L)
corresponded to a male patient with a pituitary neoplasm. PSA
chromatographic profiles from four cases with high PSA in CSF revealed
a variation with respect to the PSA immunoreactive subfractions.
Specifically, the only PSA subfraction detected for a female case whose
total PSA was the highest in this study (382 ng/L) was F-PSA (33 kDa).
The other three cases, whose CSF was of male origin, had the PSA-ACT
complex (100 kDa).
The limited diagnostic utility of most CSF biochemical analytes due to such variables as patient's age, bloodCSF barrier competence, and neurological disease states has been reviewed elsewhere (9). Our data are consistent with the proposal that PSA in the positive CSFs originated from brain tissue for three reasons. First, we found an equal number of positive CSFs among men and women. Spillover from serum is unlikely because men have about 5001000-fold higher PSA serum concentrations than do women (8). Second, the PSA concentrations found in CSF are similar in men and women. Third, the highest PSA concentration was observed in the CSF of a woman with multiple sclerosis.
The majority of our CSFs belonged to patients with multiple sclerosis, and in this group the PSA positivity was ~5%. Although the number of patients in the other categories is small, it is interesting that 3 of 4 patients with cerebral vasculitis, 2 of 3 patients with myelopathy, and 2 of 6 patients with HIV infection were positive.
This report further adds to the notion that PSA is a ubiquitous molecule and demonstrates that PSA may be produced by brain tissue. The role of PSA in CSF is currently unknown (10)(11).
References
The following articles in journals at HighWire Press have cited this article:
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S. D Mulder, J. A Heijst, C. Mulder, F. Martens, C E. Hack, P. Scheltens, M. A Blankenstein, and R. Veerhuis CSF levels of PSA and PSA-ACT complexes in Alzheimer's disease Ann Clin Biochem, November 1, 2009; 46(6): 477 - 483. [Abstract] [Full Text] [PDF] |
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F. Mannello, M. Malatesta, F. Luchetti, S. Papa, S. Battistelli, and G. Gazzanelli Immunoreactivity, Ultrastructural Localization, and Transcript Expression of Prostate-specific Antigen in Human Neuroblastoma Cell Lines Clin. Chem., January 1, 1999; 45(1): 78 - 84. [Abstract] [Full Text] [PDF] |
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F. Mannello, F. Luchetti, E. Falcieri, S. Papa, and G. Gazzanelli Prostate-specific Antigen Expression in Neuroblastoma Cell Lines Clin. Chem., June 1, 1998; 44(6): 1362 - 1363. [Full Text] [PDF] |
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T. J. Wang, H. G. Rittenhouse, R. L Wolfert, C. M. Lynne, and N. L. Brackett PSA Concentrations in Seminal Plasma Clin. Chem., April 1, 1998; 44(4): 895 - 896. [Full Text] |
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