Serum total and free prostate-specific antigen for breast cancer diagnosis in women.

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 alpha 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 alpha 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 microgram/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 (approximately 20%); however, free PSA as the predominant molecular form shows a high diagnostic specificity (approximately 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.

[1]  U. Stenman,et al.  Characterization of monoclonal antibodies for prostate-specific antigen and development of highly sensitive free prostate-specific antigen assays. , 1999, Clinical chemistry.

[2]  E. Diamandis,et al.  Prostate-specific antigen production in the female breast: association with progesterone. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[3]  E. P. Diamandis,et al.  Is prostate-specific antigen present in female serum? , 1998, Clinical chemistry.

[4]  W. Catalona,et al.  Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. , 1998, The Journal of urology.

[5]  P. Newcomb,et al.  Insulin-like Growth Factor-binding Protein (IGFBP-3) Predisposes Breast Cancer Cells to Programmed Cell Death in a Non-IGF-dependent Manner* , 1997, The Journal of Biological Chemistry.

[6]  E. Diamandis,et al.  Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases. , 1997, British Journal of Cancer.

[7]  W. Lichtenegger,et al.  Mammary serum antigen (MSA), Ca 549, CA 15-3 and CEA in breast cancer preoperative sensitivity and correlation to prognostic factors. , 1997, Anticancer research.

[8]  A. Akdaş,et al.  The role of free prostate-specific antigen in the diagnosis of prostate cancer. , 1997, British journal of urology.

[9]  E. Diamandis,et al.  Nonprostatic sources of prostate-specific antigen. , 1997, The Urologic clinics of North America.

[10]  V. Kosma,et al.  Serum tumour markers CEA, AFP, CA 15-3, TPS and Neu in diagnosis of breast cancer. , 1997, Anticancer research.

[11]  J. Forbes.  The incidence of breast cancer: the global burden, public health considerations. , 1997, Seminars in oncology.

[12]  E. Diamandis,et al.  Steroid hormone regulation of prostate-specific antigen gene expression in breast cancer. , 1997, British Journal of Cancer.

[13]  J. Ferguson,et al.  SPECIAL ARTICLE National Institutes of Health Consensus Development Conference Statement: Breast Cancer Screening for Women Ages 40-49, January 21-23, 1997 , 1997 .

[14]  E. Diamandis,et al.  Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[15]  L. Forétova,et al.  Prostate-specific antigen in nipple aspirate , 1996, The Lancet.

[16]  E. P. Diamandis,et al.  Diagnostic value of molecular forms of prostate-specific antigen for female breast cancer. , 1996, Clinical biochemistry.

[17]  E. Diamandis,et al.  Ultrasensitive detection of prostate-specific antigen by a time-resolved immunofluorometric assay and the Immulite immunochemiluminescent third-generation assay: potential applications in prostate and breast cancers. , 1996, Clinical chemistry.

[18]  S. Moss,et al.  Screening for Cancer of the Breast , 1996 .

[19]  M. Webber,et al.  Prostate-specific antigen, a serine protease, facilitates human prostate cancer cell invasion. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[20]  D. Katsaros,et al.  Prostate-specific antigen in serum of women with breast cancer. , 1995, British Journal of Cancer.

[21]  P. Sismondi,et al.  Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer. , 1995, Cancer research.

[22]  E. Diamandis,et al.  Original Articles: Prostate Cancer: Measurement of Serum Prostate Specific Antigen Levels in Women and in Prostatectomized Men With an Ultrasensitive Immunoassay Technique , 1995 .

[23]  Z. Gucev,et al.  Antiproliferative actions of insulin-like growth factor binding protein (IGFBP)-3 in human breast cancer cells. , 1995, Progress in growth factor research.

[24]  E. Diamandis,et al.  Prostate-specific antigen in milk of lactating women. , 1995, Clinical chemistry.

[25]  C. Croce,et al.  Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors. , 1994, Cancer research.

[26]  D. Peehl,et al.  Biological effects of prostate specific antigen as an insulin-like growth factor binding protein-3 protease. , 1994, The Journal of endocrinology.

[27]  E. Diamandis,et al.  Immunoreactive prostate-specific antigen levels in female and male breast tumors and its association with steroid hormone receptors and patient age. , 1994, Clinical biochemistry.

[28]  R. Rosenfeld,et al.  Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. , 1993, The Journal of biological chemistry.

[29]  E. Kawinski,et al.  Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-beta and a proteolytic modulation of cell adhesion receptors. , 1993, Biochemical and biophysical research communications.

[30]  D. Armbruster,et al.  Prostate-specific antigen: biochemistry, analytical methods, and clinical application. , 1993, Clinical chemistry.

[31]  L. Giudice,et al.  Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma. , 1992, The Journal of clinical endocrinology and metabolism.

[32]  E. Diamandis,et al.  Enzymatically amplified time-resolved fluorescence immunoassay with terbium chelates. , 1992, Analytical chemistry.

[33]  O. Nilsson,et al.  Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. , 1991, Clinical chemistry.

[34]  J. Oesterling,et al.  Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. , 1991, The Journal of urology.

[35]  U. Stenman,et al.  A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. , 1991, Cancer research.

[36]  H. Lilja,et al.  Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. , 1987, The Journal of clinical investigation.

[37]  H. Lilja.  A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. , 1985, The Journal of clinical investigation.

[38]  S. Geller,et al.  Homology between the female paraurethral (Skene's) glands and the prostate. Immunohistochemical demonstration. , 1984, Archives of pathology & laboratory medicine.

[39]  J. Pollen,et al.  Immunohistochemical identification of prostatic acid phosphatase and prostate specific antigen in female periurethral glands. , 1984, Urology.

[40]  G. Murphy,et al.  Prostate antigen: A new potential marker for prostatic cancer , 1981, The Prostate.

[41]  G. Murphy,et al.  Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay. , 1980, Cancer research.

[42]  H. Bloom,et al.  Histological Grading and Prognosis in Breast Cancer , 1957, British Journal of Cancer.