Abstract
Prostate-specific antigen (PSA) is a glycoprotein produced by the epithelial cells of the prostate. PSA is currently used in clinical practice to facilitate diagnosis and monitoring of prostate carcinoma. The prostate is an organ that possesses androgen, estrogen, and progesterone receptors, and in this respect is similar to the breast. We postulated that breast tumors might also have the ability to produce PSA. We performed these studies on a collection of 525 tumor specimens collected for routine biochemical determination of estrogen and progesterone receptors. Using a highly sensitive immunofluorometric procedure, we measured the p53 tumor suppressor gene product and PSA. Twenty nine percent of the breast tumor extracts contained detectable levels of PSA immunoreactivity (> 0.05 µg/L). The immunoreactive PSA content was associated with estrogen and/or progesterone receptor-positive tumors (P < 0.002). No association was found between PSA immunoreactivity and levels of the p53 tumor suppressor gene product (P = 0.37). High performance liquid chromatography and Western blot analysis revealed that the PSA immunoreactivity in the tumor had a molecular weight of 30 kDa, similar to that of seminal PSA. Immunoreactive PSA-positive tumors were associated with younger women (P = 0.012) and earlier disease stage (P = 0.064). We postulate that PSA immunoreactivity may be an additional marker of steroid hormone receptor-ligand action.
References
Carter HB, Coffey DS: The prostate: an increasing medical problem. The Prostate 16: 39–48, 1990
Nomura AMY, Kolonel LN: Prostate cancer: a current perspective. Am J Epidemiol 13: 200–227, 1991
Bruchovsky N, Brown EM, Coppin CM,et al.: The endocrinology and treatment of prostate tumor progression. Prog Clin Biol Res 239: 347–357, 1987
Thompson TC: Growth factors and oncogenes in prostate cancer. Cancer Cells 2: 345–354, 1990
Oesterling JE: Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol 145: 907–923, 1991
Diamandis EP: Immunoassays with time-resolved fluorescence spectroscopy. Principles and applications. Clin Biochem 21: 139–150, 1988
Yu H, Diamandis EP: Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies. Clin Chem 39: 2108–2114, 1993
Harris JR, Lippman ME, Veronesi U, Willett W: Breast cancer, (first of three parts). New Engl J Med 327: 319–328, 1992
Harris JR, Lippman ME, Veronesi U, Willett W: Breast cancer, (second of three parts). New Engl J Med 327: 390–398, 1992
Harris JR, Lippman ME, Veronesi U, Willett W: Breast cancer, (third of three parts). New Engl J Med 327: 473–480, 1992
McGuire WL, Clark GM: Prognostic factors and treatment decisions in axillary node-negative breast cancer. New Engl J Med 326: 1756–1761, 1992
McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM: How to use prognostic factors in axillary nodenegative breast cancer patients. J Natl Cancer Inst 82: 1006–1015, 1990
Muss HB: Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat 21: 15–26, 1992
Hassapoglidou S, Diamandis EP, Sutherland DJA: Quantification of p53 protein in tumor cell lines, breast tissue extracts and serum with time-resolved immunofluorometry. Oncogene 8: 1501–1509, 1993
Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O: A complex between prostate-specific antigen and α1-antichymotrypsin is the major form of prostatespecific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res 51: 222–226, 1991
Lilja H, Christensson A, Dahlen U,et al.: Prostate-specific antigen in serum occurs predominantly in complex with α1-antichymotrypsin. Clin Chem 37: 1618–1625, 1991
Ford TF, Butcher DN, Masters JRW, Parkinson CM: Immunocytochemical localisation of prostate-specific antigen: specificity and application to clinical practice. Br J Urol 57: 50–55, 1985
Papotti M, Paties C, Peveri V, Moscuzza L, Bussolati G: Immunocytochemical detection of prostate-specific antigen (PSA) in skin adnexal and breast tissues and tumors. Bas Appl Histochem 33: 25–29, 1989
Slamon DJ, Clark GM, Wong SG,et al.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182, 1987
Bryan RM, Mercer RJ, Bennett RC, Rennie GC, Lie TH, Morgan FJ: Androgen receptors in breast cancer. Cancer 54: 2436–2440, 1984
Wolf DA, Schulz P, Fittler F: Transcriptional regulation of prostate kallikrein-like gene by androgen. Mol Endocrinol 6: 753–762, 1992
Henttu P, Liao SS, Vihko P: Androgens up-regulate the human prostate-specific antigen messenger ribonucleic acid (mRNA) but down-regulate the prostatic acid phosphatase mRNA in the LNCaP cell line. Endocrinology 130: 766–772, 1992
Montgomery BT, Young CY, Bilhartz DL, Andrews PE, Prescott JL, Thompson NF: Hormonal regulation of prostate-specific antigen (PSA) glycoprotein in the human prostate adenocarcinoma cell line, LNCaP. Prostate 21: 63–73, 1992
Weber JP, Oesterling JE, Peters CA, Partin AW, Chan DW, Walsh PC: The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostate hyperplasia. J Urol 141: 987–991, 1989
Wei LL: Transcriptional activation of the estrogen receptor. Clin Chem 39: 341–345, 1993
Milgrom E: The oestrogen-regulated pS2-BCEI protein in breast cancer. In: Goldhirsch A (ed) Endocrine Therapy of Breast Cancer V. Springer Verlag, Berlin, 1992, pp 17–22
Foekens JA, Rio MC, Seguin P,et al.: Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res 50: 3832–3837, 1990
Rochefort H: Cathepsin D in breast cancer. Breast Cancer Res Treat 16: 1–13, 1990
Silvestrini R, Veneroni S, Benini E, DiFronzo G, Daidone MG: p53 and cathepsin D are independent of established prognostic factors in breast cancer. Int J Oncol 1: 507–512, 1992
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Diamandis, E.P., Yu, H. & Sutherland, D.J.A. Detection of prostate-specific antigen immunoreactivity in breast tumors. Breast Cancer Res Tr 32, 301–310 (1994). https://doi.org/10.1007/BF00666007
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DOI: https://doi.org/10.1007/BF00666007