Faculty Bibliography

OBJECTIVE: To evaluate the growth pattern of the large uterine leiomyomata (ULM), we examined the spatial gene distributions, vessel density, proliferative activity, and hyaline degeneration. DESIGN: Tissue sections from three-dimensional large ULM, matched myometrium, and small ULM were collected and microarrayed. The spatial difference of the tumor activity was mapped in large ULM. SETTING: University clinical research laboratory. PATIENT(S): Hysterectomy specimens from 7 patients with large (>10 cm) ULM and 3 patients with large (>10 cm) uterine leiomyosarcomas. INTERVENTION(S): Tissue microarray analysis by the immunohistochemistry. MAIN OUTCOME MEASURE(S): Selected gene products, vessel density, and the percentage of hyaline degeneration were all scored in tissue cores/sections of large and small ULM against matched myometrium. RESULT(S): We found that there was a spherical spatial difference of the tumor activities in large ULM. The tumor region next to the periphery, the most biologically active zone, demonstrated higher levels of gene expression, a higher density of vessels, a higher proliferative rate and a lower level of hyaline degeneration. The large ULM have higher levels of gene products (except for estrogen and progesterone receptors) than small ULM. CONCLUSION(S): In comparison of the spatial patterns of the gene activity between the large ULM and the large uterine leiomyosarcoma, the large ULM illustrate a growth pattern of nutritional dependence

BACKGROUND: Black ethnicity is one of the risk factors for uterine leiomyomata (ULM). Little is known about the ethnic differences in leiomyoma-associated gene products in women with uterine leiomyomata. METHODS: A total of 120 hysterectomies with ULM were collected from black, Asian, Hispanic and white women (30 cases from each group). Twenty-two gene products were selected for the study. The expressions of the selected dysregulated gene products were measured by the semiquantification and the immunoscores were normalized by matched myometrium. RESULTS: The relative expressions of progesterone receptor A (PR-A) (up-regulation), retinoid acid receptor alpha (down-regulation), and retinoid X receptor alpha (RXRalpha) (no change) in leiomyomata compared to normal myometrium in black women were significantly different compared to other ethnic groups (P < 0.05). About one-third of ULM from black women subclustered together in association with a group of up-regulated gene products. Many other gene products, including local growth factors, insulin-like growth factor (IGF)-signalling proteins, and cell proliferation markers, were dysregulated in ULM but showed non-significant differences between the ethnic groups. CONCLUSIONS: There are substantial differences of the sex steroid receptors and other nuclear receptors between black women and other ethnic groups. Based on tissue microarray data, there are at least two broad groups of leiomyomata presented by the dysregulation of different groups of gene products. One is dominated by up-regulation of amplified in breast cancer 1, CD24, hamartin, human mobility group gene 2, IGF2, PR-A and RXR, and the other is characterized by up-regulation of epithelial growth factor receptor, down-regulation of hamartin, PR-A and tuberin