Breast Cancer Research and Treatment 38: 247-252, 1996. © 1996 Kluwer Academic Publishers. Printed in the Netherlands. Report Quantification of prostate-specific antigen immunoreactivity in human breast cyst fluids Ferdinando Mannello,~GianDomenico Bocchiotti,2 Giuseppe Bianchi,3Francesco Marcheggiani,~and Giancarlo Gazzanelli~ 1Institute of Histology and Laboratory Analysis, University of Urbino, Urbino, Italy; 2 Centre for Study and Prevention of Breast Diseases, Hospital of Acqui, Acqui Terme, Italy;7 Laboratory of lmrnunology, Hospital of Urbino, Italy Key words: breast cyst fluid, electrolyte, gross cytic breast disease, prostate specific antigen Summary The frequency of gross cystic breast disease in premenopausal women and its possible association with in- creased breast cancer risk emphasises the importance of investigations relating to breast cyst fluid composi- tion. In order to contribute to a better analysis of this medium, we have measured the presence of prostate- specific antigen immuno-reactivity in sixty-four human breast cyst fluids. Data analyses show that 35 % of samples presented a level of this antigen < 0.05 gg/L, whereas 42 out of 64 cysts show a significant increase in the mean value of metabolically active apocrine cysts when compared to flattened cysts (p < 0.01). We report the first evidence that breast epithelium of gross cysts produces, secretes, and accumulates large amounts of prostate-specific antigen, a glycoprotein produced by prostatic tissue but recently detected in breast turnouts, normal tissues, and during pregnancy. The production and intracystic accumulation of this serine protease in biosynthetically active apocrine type cyst can play a feasible role in the naturalhistory of gross cystic breast disease as well as in the mechanism of cyst formation, enlargement, and transformation. Introduction Gross cystic breast disease (GCBD) is the common- ly occurring benign disease of the breast in preme- nopausal women, with a frequency of about 7% [1]. Although breast cystic lesions are not considered to be precancerous, several studies indicate that the patients with GCBD have a 2- to 4-fold greater risk of developing breast cancer than control popula- tions [2, 3]. It is surprising that no biochemical analysis of the GCBD fluid was reported prior to 1973, even though this pathology has been recognised as a fre- quent clinical entity of the breast since 1845 [4]. In recent years, novel approaches to this issue have been offered by studies on the biochemical aspects of breast cyst fluid (BCF), and several reviews are available on protein, hormone, and electrolyte con- tent [5-7]. The biochemical composition of BCF has been studied in an attempt to understand the mecha- nisms involved in cyst formation and to define their possible role in carcinogenesis; these analyses have pointed out that most parameters show a bimodal distribution. The consistency of these analyses has led to identification of two main categories of cysts, Address for offprints: E Mannello, Istituto di Istologia ed Analisi di Laboratorio, Universitfi Studi, FacoltS, di Science MFN, Via Zeppi, 61029, Urbino, Italy