The role of hypoxia related angiogenesis in uterine smooth muscle tumors.

Mechanisms of hypoxia-related angiogenesis are important for uterine smooth muscle tumors. Factors that are related to angiogenesis during hypoxia include vascular endothelial growth factor (VEGF), hypoxia inducible factor 1α (HIF1α), T-cell intracellular antigen1 (TIA1), eukaryotic translation initiation factor 2α (eIF2α) and thrombospondin 1 (TSP1). We investigated immunoreactivities of VEGF, HIF1α, TIA1, eIF2α and TSP1 using an indirect immunoperoxidase method for formalin fixed, paraffin embedded tumors that had been diagnosed as leiomyoma (LMY), cellular leiomyoma (CLM) or leiomyosarcoma (LMS). TSP1 immunoreactivity was scored as moderate, mild or minimal, while VEGF, eIF2α and TIA1 immunoreactivities were scored as mild, moderate and strong in LMY, CLM and LMS samples, respectively. HIF1α immunoreactivity was scored as mild to minimal in LMY, CLM and LMS samples, but showed no statistically significant differences among samples. Although angiogenic factors showed strong immunohistochemical staining intensity in LMS, anti-angiogenic factors showed minimal immunohistochemical intensity. There was no difference in HIF-1α immunoreactivity compared to LMY, CLM and LMS samples. We suggest that HIF1α protein synthesis could be suppressed by eIF2α and TIA1. Furthermore, VEGF could be activated by pathways such as COX2, Ras, NF-ĸB or c-myc instead of HIF1α. Angiogenesis could trigger and accelerate tumor development; therefore, anti-angiogenic therapy could be useful for treatment of tumors.

Completely infarcted smooth muscle tumor of the placental membrane.

Non-trophoblastic tumor of the placenta is rare, and so is placental smooth muscle tumor. We report leiomyoma of the placental membrane, which was discovered on cesarean section. Histologically, the tumor was a benign leiomyoma with complete necrosis, and this finding was confirmed immunohistochemically. Only six cases of smooth muscle tumors of the placenta have been reported to date. This is the third report of leiomyoma involving the placental membrane.

Expression of thrombospondin 1 (TSP 1) in patients with uterine smooth muscle tumors: an immunohistochemical study.

OBJECTIVE: Angiogenesis is an essential component for tumor development regulated by both proangiogenic and antiangiogenic factors. Thrombospondin 1 (TSP 1) suppresses angiogenesis by inhibiting endothelial cell proliferation and inducing endothelial cell apoptosis. The aim of this study was to compare the expression of TSP 1 in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP) and leiomyosarcoma (LMS). Furthermore, we evaluated the prognostic relevance of TSP 1 in uterine LMS. METHODS: TSP 1 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP and in 21 patients with LMS. Standard immunohistochemical techniques were used to study the expression of TSP 1 in 5-mum-thick tumor sections. TSP 1 expression was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis. RESULTS: TSP 1 was expressed in 77% of leiomyomas, in 13% of STUMP and in 24% of LMS. A statistically significant difference regarding the frequency of TSP 1 expression was observed between leiomyoma and LMS (P < 0.05) as well as between leiomyoma and STUMP (P < 0.05), but not between LMS and STUMP (P > 0.05). Furthermore, a statistically significant correlation between vascular space involvement and TSP 1 expression was observed in patients with uterine LMS, with patients without vascular space involvement having more frequently TSP 1 positive tumors (P = 0.04). No statistically significant correlation between TSP 1 and clinical stage, age and recurrence disease could be detected (P > 0.05). CONCLUSIONS: We found that TSP 1 was more frequently expressed in leiomyoma compared to STUMP and LMS. Additionally, the statistically significant negative correlation between vascular space involvement and TSP 1 expression in patients with uterine LMS shows that TSP 1 might work as a predictive factor in patients with LMS. Further clinical studies are necessary to prove our results and to clarify the role of TSP 1 in uterine smooth muscle tumors.