Akademik Veri Yönetim Sistemi
The Journal of clinical endocrinology and metabolism, cilt.109, sa.7, ss.1765-1772, 2024 (SCI-Expanded)
Context Approximately 150 patients with juvenile gigantomastia have been reported in the literature but the underlying biologic mechanisms remain unknown. Objective: To conduct extensive clinical, biochemical, immunochemical, and genetic studies in 3 patients with juvenile gigantomastia to determine causative biologic factors. Methods: We examined clinical effects of estrogen by blockading estrogen synthesis or its action. Breast tissue aromatase expression and activity were quantitated in 1 patient and 5 controls. Other biochemical markers, including estrogen receptor alpha (ER alpha), cyclin D1 and E, p-RB, p-MAPK, p-AKT, BCL-2, EGF-R, IGF-IR beta, and p-EGFR were assayed by Western blot. Immunohistochemical analyses for aromatase, ER alpha and beta, PgR, Ki67, sulfotransferase, estrone sulfatase, and 17 beta HD were performed in all 3 patients. The entire genomes of the mother, father, and patient in the 3 families were sequenced. Results: Blockade of estrogen synthesis or action in patients resulted in demonstrable clinical effects. Biochemical studies on fresh frozen tissue revealed no differences between patients and controls, presumably due to tissue dilution from the large proportion of stroma. However, immunohistochemical analysis of ductal breast cells in the 3 patients revealed a high percent of ER alpha (64.1% +/- 7.8% vs reference women 9.6%, range 2.3-15%); aromatase score of 4 (76%-100% of cells positive vs 30.4% +/- 5.6%); PgR (69.5% +/- 15.2% vs 6.0%, range 2.7%-11.9%) and Ki67 (23.7% +/- 0.54% vs 4.2%). Genetic studies were inconclusive although some intriguing variants were identified. Conclusion: The data implicate an important biologic role for ER alpha to increase tissue sensitivity to estrogen and aromatase to enhance local tissue production as biologic factors involved in juvenile gigantomastia.