Quantification of vascular endothelial growth factor-A in leiomyomas and adjacent myometrium

Abstract

Although uterine leiomyomas constitute the commonest benign tumour in women, the regulation of their growth is poorly understood. It is believed that angiogenesis, the process by which new capillaries develop from pre-existing blood vessels, may be involved. We therefore investigated the expression of vascular endothelial growth factor-A (VEGF-A), a primary regulator of angiogenesis, in leiomyoma tissue and the adjacent myometrium in 36 pre-menopausal women undergoing hysterectomy for leiomyomas, with or without prior treatment with gonadotrophin-releasing hormone analogue (GnRHa). In 5 microm sections prepared from archival paraffin-wax blocks, VEGF-A was demonstrated by standard immunohistochemistry using a monoclonal antibody. VEGF-A was expressed in 14 of 18 (77.8%) leiomyoma sections from women without GnRHa pretreatment, and in 15 of 18 (83%) of those from women with prior treatment. VEGF-A expression in the adjacent myometrium was much lower, being noted in two of 18 (11.1%) sections from women without prior GnRHa treatment and in one of 18 (5.5%) sections from tissue that had been subject to prior down-regulation. Moreover, when VEGF-A expression was present, expression was strong in leiomyomas (> or =20 focal areas/cm(2)), but not in adjacent myometrium. The differential expression of VEGF-A antigen in leiomyomas compared with the adjacent myometrium indicates that local angiogenesis may be important in the development and growth of these tumours. GnRHa therapy does not appear to alter this pattern of VEGF-A expression.

Adenovirus-Mediated Delivery of a Dominant-Negative Estrogen Receptor Gene in Uterine Leiomyoma Cells Abrogates Estrogen- and Progesterone-Regulated Gene Expression

“…VEGF is critical for the initiation and maintenance of the angiogenic response, a major process by which new blood vessels are formed in the adult (67). Uterine leiomyomas were reported to express the VEGF protein (10,68,69), which is regulated by estrogen as well (9) and has been implicated in leiomyoma growth (68,69). Our study demonstrates that Ad-DNER decreases the expression of the VEGF protein in a dose-dependent manner in leiomyoma cells (Fig.…”

“…Induction of cyclin D1 expression is a critical feature of the mitogenic action of estrogen (8). Other potential mechanisms by which estrogen stimulates the proliferation and growth of uterine leiomyomas involve the regulation of the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) (9), which is highly expressed in leiomyoma tissues compared with the normal adjacent myometrium (10).…”

Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

“…Several growth factors, including epidermal (EGF) [9], insulin-like (IGF) [10,11], vascular endothelial (VEGF) [12], platelet-derived (PDGF) [13], and transforming (TGF)-β growth factors [14], are associated with leiomyoma growth. Furthermore, some apoptotic factors such as p53 tumor suppressor [15], B-cell lymphoma (Bcl)-2 [16,17], and tumor necrosis factor (TNF)-α [18] are involved in leiomyoma apoptosis.…”

Clinicopathologic markers of uterine leiomyosarcoma originating from smooth muscle tumors of low malignancy

“…Since the establishment of nutrient blood vessels is fundamental to growth of all tumors, it has been suggested that angiogenesis may play a role in the regulation of tumor growth. Gentry et al [20] reported a different expression of VEGF antigens in LM compared with the adjacent myometrium, suggesting that local angiogenesis may be important in the development and growth of these mesenchymal tumors. Also, since uterine LMS has a propensity for hematogeneous spread, we hypothesized different VEGF expressions to be present among phenotypically different smooth muscle tumors.…”

“…VEGF is a primary regulator of angiogenesis [20]. Since the establishment of nutrient blood vessels is fundamental to growth of all tumors, it has been suggested that angiogenesis may play a role in the regulation of tumor growth.…”