Breast development gives insights into breast disease

AIMS: Studies of developing human breasts are essential for understanding the organogenesis as well as molecular pathogenesis of benign and malignant breast diseases. In this study we have examined the distribution of TGF-alpha, TGF-beta 1, tenascin-C and collagen type IV with the aim of starting to build a picture of the profile of molecules that may be involved in the development of the human breast. METHODS AND RESULTS: Ten fetal breasts (16 to 23 weeks of gestation) and 45 infant breasts, ranging in age from newborn to 2 years, were used in this study. Paraffin sections from these samples were immunostained with antibodies for these proteins and for Ki67 to elucidate the level of proliferative activity in different stages of breast development. TGF-alpha immunoreactivity was observed both in the stromal and the epithelial cells within fetal and infant breasts up to 25 days. TGF-beta 1 immunoreactivity was localized in the extracellular matrix. Tenascin-C was found around the neck of the developing breast bud and in the extracellular matrix of the infant with peaks in the newborn at 6-12 weeks. The immunoreactivity for type IV collagen was more intense in the region of the breast bud neck in the fetal breasts and reduced around the tips of lobular and terminal-end buds within the infant breasts. CONCLUSIONS: The distribution of the growth factors and extracellular matrix proteins within the developing human breast indicates that they play a significant role in different cellular compartments during morphogenesis and provides insights into breast disease.