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This study evaluated bone morphogenetic protein-2 (BMP2) expression patterns in uterine smooth muscle tumors and other uterine tissues using immunohistochemistry. The researchers found that BMP2 was expressed in a minority of leiomyosarcomas and leiomyomata, while it was largely absent in normal myometrium, endometrium, and specific benign conditions. Importantly, the analysis revealed no significant difference in clinical outcomes or tumor characteristics between BMP2-positive and BMP2-negative leiomyosarcomas, indicating a lack of prognostic value for this marker. Relevance to endometriosis: adenomyosis is explicitly mentioned as one of the tissues evaluated where BMP2 was not expressed, though the paper's primary focus remains on uterine smooth muscle tumors rather than these conditions.
Abstract
Bone morphogenetic proteins (BMPs) are extracellular, multifunctional growth factors that constitute the largest subset of the transforming growth factor β superfamily. BMP2 is involved in cardiovascular embryogenesis, in addition to a variety of other postnatal functions, such as neovascularization, osteoinduction, tumor signaling, and in the uterus, stromal decidualization at the implantation site. Estrogen receptor signaling is common in smooth muscle tumors of the uterus, and preclinical models suggest significant interactions between BMP2 and estrogen receptor-mediated signaling. The purpose of this study is to define the patterns of BMP2 expression, as assessed by immunohistochemistry, in smooth muscle tumors and other tissues of the uterine corpus, and to establish whether BMP2 expression has any prognostic significance in uterine leiomyosarcomas. BMP2 was positive (cytoplasmic pattern, typically focal) in 24% of leiomyosarcomas and 20.7% of leiomyomata, but was either infrequently expressed or not expressed in all other tissues evaluated, including normal myometrium and endometrium, endometrial stromal tumors, typical adenomyoma, adenomyosis, and serosal endometriosis. The endothelial cells of small, thin-walled vessels were frequently, but not invariably immunoreactive for BMP2. There was no significant difference between BMP2⁺ and BMP⁻ leiomyosarcomas regarding average tumor size, average patient age, microvessel density, and proportions with high tumor grade, advanced stage and frequency of death from disease on follow-up. Two (29%) of 7 BMP2⁺ leiomyosarcomas were estrogen receptor+, compared with 5 (50%) of 10 BMP2⁻ leiomyosarcomas, a statistically insignificant difference (P=0.62). It is concluded that BMP2 is only expressed in a minority of smooth muscle tumors of the uterine corpus, and lacks prognostic significance in leiomyosarcomas. BMP2 is rarely expressed in the other nonendothelial tissues of the human uterine corpus that were evaluated. The significance of frequent BMP2 expression in small vessels of the uterus requires further investigation.
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Patterns of Bone Morphogenetic Protein-2 Expression in Smooth Muscle Tumors of the Uterine Corpus and Other Uterine Tissues
- Oluwole Fadare
- Idris L. Renshaw
- Sharon X. Liang
Bone morphogenetic proteins (BMPs) are extracellular, multifunctional growth factors that constitute the largest subset of the transforming growth factor β superfamily. BMP2 is involved in cardiovascular embryogenesis, in addition to a variety of other postnatal functions, such as neovascularization, osteoinduction, tumor signaling, and in the uterus, stromal decidualization at the implantation site. Estrogen receptor signaling is common in smooth muscle tumors of the uterus, and preclinical models suggest significant interactions between BMP2 and estrogen receptor-mediated signaling. The purpose of this study is to define the patterns of BMP2 expression, as assessed by immunohistochemistry, in smooth muscle tumors and other tissues of the uterine corpus, and to establish whether BMP2 expression has any prognostic significance in uterine leiomyosarcomas. BMP2 was positive (cytoplasmic pattern, typically focal) in 24% of leiomyosarcomas and 20.7% of leiomyomata, but was either infrequently expressed or not expressed in all other tissues evaluated, including normal myometrium and endometrium, endometrial stromal tumors, typical adenomyoma, adenomyosis, and serosal endometriosis. The endothelial cells of small, thin-walled vessels were frequently, but not invariably immunoreactive for BMP2. There was no significant difference between BMP2+ and BMP− leiomyosarcomas regarding average tumor size, average patient age, microvessel density, and proportions with high tumor grade, advanced stage and frequency of death from disease on follow-up. Two (29%) of 7 BMP2+ leiomyosarcomas were estrogen receptor+, compared with 5 (50%) of 10 BMP2− leiomyosarcomas, a statistically insignificant difference (P=0.62). It is concluded that BMP2 is only expressed in a minority of smooth muscle tumors of the uterine corpus, and lacks prognostic significance in leiomyosarcomas. BMP2 is rarely expressed in the other nonendothelial tissues of the human uterine corpus that were evaluated. The significance of frequent BMP2 expression in small vessels of the uterus requires further investigation.
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