Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intr auterine hormonal status, especially a change in estrogen status, could pre dispose to carcinogenesis. In an attempt to achieve new information on earl y breast growth, a series of developing human breasts have been analyzed, n amely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts ( 7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphol ogical features, we studied the immunohistochemical expression of some mark ers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progester one (PR) receptors for hormonal profile, and smooth-muscle actin for myoepi thelial differentiation. The results were as follows: (a) lobules, absent b etween 28 weeks and 2 days, were well evident at 2 years of age and at pube rty; (b) myoepithelial cells appeared from 28 weeks onward and persisted la ter with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two differ ent patterns: periductal vascularization (PDV) and interductal vascularizat ion (IDV), IDV being always present, whereas PDV was found only in infant b reasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; ( g) stromal cells had no hormonal receptors and were heterogeneous for proli feration and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial co mpartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.