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Molecular Oncology, Markers, Clinical Correlates |
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1X5 Canada [M. H. B., E. P. D]; Department of Gynecologic Oncology, Institute of Obstetrics and Gynecology, University of Turin, 10121 Turin, Italy, [M. G., R. P., P. S.]; and Department of Medicine, Louisiana State University Medical Center, Shreveport, Louisiana 71130 [H. Y.]
Prostate-specific
antigen (PSA) is a serine protease expressed at high levels in prostate
epithelium, and elevated PSA in serum is a well-established marker of
prostate cancer. Recently, the relative proportions of free PSA and PSA
complexed to the serine protease inhibitor
1-antichymotrypsin have become important variables in
distinguishing between prostate cancer and benign prostatic
hyperplasia. Numerous studies have demonstrated the production of PSA
in female tissues such as the breast, and low levels of PSA are present
in female sera. The objective of this study was to measure and compare
the relative proportions of free PSA and PSA complexed to the serine
protease inhibitor 1-antichymotrypsin in the serum of
women with breast cancer or benign breast disease or women with no
known malignancies. PSA was measured with an established immunoassay
for total PSA and a novel immunoassay for free PSA, both of which had a
detection limit of 0.001 µg/liter (1 ng/liter). The percentage of
breast cancer patients with free PSA as the predominant molecular form
(>50% of total PSA) in serum was five times higher than that of
healthy women or women with benign breast disease, and PSA decreased in
the serum of breast cancer patients after surgery. The diagnostic use
of free PSA for breast cancer is limited at this point, due to the low
diagnostic sensitivity (
20%); however, free PSA as the predominant
molecular form shows a high diagnostic specificity (96%) in
comparison to women free of breast cancer or with benign breast
disease. These results suggest that the clinical applicability of free
PSA for breast cancer diagnosis and the biological mechanism behind its
increase should be further investigated.
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