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Technical Briefs |
1
Ist. Istol. & Anal. Lab., Facoltà Sci., MFN Università, Via E. Zeppi, 61029 Urbino, Italia;
2
Div. Med., and
3
Lab. Anal. Ospedale Civile, Urbino, Italia;
a author for
correspondence: fax +39-722-322370, e-mail citometria{at}fis.uniurb.it
Prostate-specific antigen (PSA) is a serine protease, first
identified in 1970 (1) and nowadays widely used for early
detection and monitoring of prostate cancer (2). Although
previously thought to be produced exclusively by the epithelial cells
of the prostate (3), at present PSA is considered a
widespread biochemical marker produced and secreted in several
biological fluids, by both normal and tumor tissues (e.g.,
(4)(5)(6)(7)(8)(9)(10)(11)(12)). In blood, complexes form between PSA
and serine protease inhibitors, such as
1-antichymotrypsin and 2-macroglobulin
(2)(3)(4). Free PSA also exists in serum, even
though its increased concentration in female serum is a matter of
recent debate (12)(13)(14)(15)(16).
Considering the immunoreactivity of PSA in tumors of the lung (7)(8), we undertook the study of the PSA distribution and expression in pleural effusions collected from 68 women, ages 60 ± 11 years.
The present work was carried out in accordance to the ethical standards of Helsinki Declaration of 1975, as revised in 1983. Clinical, radiological, and laboratory diagnoses of pleural effusions were established according to standard criteria (17)(18). The patients studied with malignancies had not yet received cytotoxic drugs or chemotherapeutic agents.
After collection, pleural fluids were centrifuged at ~19 000g for 20 min at 4 °C, and the supernatants were stored at -30 °C until processing. Blood was also drawn from the women and, after clotting, was centrifuged at 340g for 5 min at 4 °C and stored at -30 °C till assay. We quantified the PSA in 35 transudates (17 from women with congestive heart failure, 11 with liver cirrhosis, and 7 with nephrosis) and 33 exudates (21 from women with neoplasms, 8 with tuberculosis, and 4 with parapneumonia), using two commercially available kits: a solid-phase two-site IRMA (PSA-RIACTTM; CIS Bio International, Gif-sur-Yvette, France) and a MEIA (IMx®; Abbott Labs, Abbott Park, IL). The procedures for PSA determinations, performed according to manufacturer's recommendations, have been described in detail elsewhere (5)(6). The results, expressed as mean ± SE, were considered to be statistically significant at P <0.05. All statistical analyses were performed through the StatView v.4.1 package (Abacus Concepts, Berkeley, CA) on an Apple Macintosh Power PC.
Out of 68 patients examined, only 71% contained detectable amounts of
PSA: median 0.105 µg/L, mean 0.644 ± 0.171 µg/L (range
0–8.07 µg/L). To exclude possible matrix effects in the PSA assays
(from the presence of lipids and pigments in pleural fluids), we
diluted the samples having a high PSA content. The relation between PSA
content and dilution showed good linearity (y = -0.147
+ 86.5x, r = 0.958), confirming that pleural
effusion does not affect the assays' performance. We further compared
PSA values in pleural fluids obtained with PSA-RIACT (y) and
IMx-PSA (x), obtaining a regression equation of
y = 1.09x - 0.34 (r =
0.976, P <0.001). Moreover, 57 (84%) of the women showed a
plasma PSA content 
0.05 µg/L—in close agreement with literature
data (3)(15). The mean PSA concentration in
our pleural effusion samples was higher in exudates (0.977 ±
0.319 µg/L) than in transudates (0.438 ± 0.117 µg/L;
z = 1.625, P <0.01), even though 37% of
transudate and 22% of exudate pleural fluids were PSA negative. The
PSA content in pleural effusions was significantly greater than in
plasma (0.041 ± 0.009 µg/L; z = 6.759,
P <0.001), but there was no statistically significant
correlation between PSA concentration and the women's ages, even after
log-transformation.
Western blot analysis (with an anti-human PSA monoclonal antibody from
Dako, Milan, Italy) detected a major 33-kDa band corresponding to free
PSA and an infrequent minor band of 100 kDa corresponding to
1-antichymotrypsin-bound PSA; no additional
spurious bands were seen.
Two sources might account for PSA expression in pleural effusions: (a) plasma ultrafiltration and accumulation at an increased rate in the pleural space through the capillaries of inflamed pleura (plasma from patients with lung adenocarcinoma has been shown to be positive for PSA (7)), or (b) local secretion, mainly from enhanced production by neoplastic cells (adenocarcinoma and squamous cell carcinoma tissues were recently found to contain the 33-kDa (free) form of PSA (8)).
The presence of steroid receptors in pleural fluid (19) may represent another possible molecular mechanism of enhanced PSA expression in pleural effusion, probably related to the known modulation by hormones (20).
To our knowledge (after a careful review of literature), this is the first report concerning PSA in pleural effusions in concentrations measurable by commercial methods. The detectable amounts of PSA in pleural effusions give further evidence of the distinctiveness of this widespread serine protease, even though the biological effects and the mechanism(s) causing its increase remain to be elucidated. We are currently investigating the potential role of PSA in nonprostatic tissues and in other biological fluids as a possible sensitive molecular marker implicated in hormone responsiveness and (or) the inflammatory/neoplastic processes, which could in part be responsible for the proteolytic activities in pleural effusions (18)(21).
References
The following articles in journals at HighWire Press have cited this article:
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  M. Malatesta, F. Mannello, F. Luchetti, F. Marcheggiani, L. Condemi, S. Papa, and G. Gazzanelli Prostate-Specific Antigen Synthesis and Secretion by Human Placenta: A Physiological Kallikrein Source during Pregnancy J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 317 - 321. [Abstract] [Full Text]
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 F. Mannello, M. Malatesta, E. Fusco, G. Bianchi, A. Cardinali, and G. Gazzanelli Biochemical Characterization and Immunolocalization of Prostate-specific Antigen in Human Term Placenta Clin. Chem., August 1, 1998; 44(8): 1735 - 1737. [Full Text] [PDF]
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F. Mannello, M. Sebastiani, S. Amati, and G. Gazzanelli Prostate-specific antigen expression in a case of intracystic carcinoma of the breast: characterization of immunoreactive protein and literature surveys Clin. Chem., August 1, 1997; 43(8): 1448 - 1454. [Abstract] [Full Text] [PDF]
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F. Mannello, G. Miragoli, G. Bianchi, and G. Gazzanelli Prostate-Specific Antigen in Ascitic Fluid Clin. Chem., August 1, 1997; 43(8): 1461 - 1462. [Full Text]
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