Molecular Forms and Ultrastructural Localization of Prostate-specific Antigen in Nipple Aspirate Fluids,

Abstract

Prostate-specific antigen (PSA) is a member of the human kallikrein family of serine proteases that for a long time was thought to be produced exclusively by the epithelial cells of the prostate gland (1). Because of its tissue specificity, PSA has been widely used as a marker for diagnosing and monitoring prostate cancer (2). However, recent studies have demonstrated the widespread distribution of PSA in a variety of tumor types, healthy tissues, and biological fluids [reviewed in Ref. (3)]. Although the physiological role and the biological significance of extraprostatic PSA currently are unknown, it has been suggested that this serine protease should be regarded as a growth factor regulator produced by cells bearing steroid hormone receptors (4)(5). Several studies have biochemically and molecularly demonstrated that female breast produces and secretes PSA through steroid hormone regulation (in particular by androgens and progestins but not estrogens) (6)(7). Moreover, PSA has been suggested as a marker of good prognosis for women with breast cancer (8), even if there is contradictory evidence regarding this argument (9)(10). Over recent years, analysis of nipple aspirate fluids (NAFs) from nonlactating women has attracted considerable interest as a rapid and noninvasive method to assess the environment and metabolic activity within the mammary gland (11). Light microscopic studies have revealed the presence of abnormal apocrine epithelial cells in fluids from women with breast diseases, allowing the identification of women who may be at increased risk of developing breast cancer (12). Similarly, biochemical analysis of breast NAFs has demonstrated the presence of a variety of substances, including hormones, enzymes, electrolytes, proteins, and toxic compounds, that may be involved in the malignant transformation (13)(14)(15). Recent studies have demonstrated the presence of measurable amounts of total PSA in NAF, which are …