angiogenin and Uterine-Neoplasms

Leiomyosarcoma (LMS) is a relatively uncommon malignant tumour derived from smooth muscle cells that rapidly metastasizes to distant regions. It rarely reaches oral tissues in which smooth muscle tissues are absent. We report the case of a 56-year-old woman who presented with LMS in the maxilla that had metastasized from a primary tumour in her uterus, received a total hysterectomy with bilateral salpingo-oophorectomy 9 months earlier. To reveal the poor prognosis of metastatic LMS, a total of 26 antibodies against different factors related to the proliferation, apoptosis, necrosis, and angiogenesis were simultaneously applied on the immunohistochemistry and immuno-blot detection in order to screen for expression n of different proteins in the metastatic LMS. Compared with the immunoreactions of primary uterine LMS, the different antibodies for cellular proliferation, i.e., proliferating cell nuclear antigen (PCNA), multiple primary neoplasm-2 (MPN-2), Max, p21, CDK4, p53, Rb-1, Bad, Bcl-2, epidermal growth factor receptor (EGF-R), hepatocyte growth factor (HGF), C-erbb2, Maspin, and DMBT-1, and those for angiogenesis, i.e., vWF, CD31, and Angiogenin, were more intensely expressed, while Bax, p16, Wnt-1, E-cadherin, and APC were relatively weakly expressed. In particular, beta-catenin was densely localized to the nuclei of tumour cells. These data suggest that rapid proliferation of the tumour cells is related to over-expression of different oncogenes, and that the infiltrative growth and early distant metastasis of these tumour cells are related to over-expression of angiogenesis factors. A total of seven cases of metastatic LMS to the oral cavity that had been published in the English literature were reviewed, and the reason for the poor prognosis in the metastatic LMS is suggested in this case report.

Topics: bcl-Associated Death Protein; beta Catenin; Calcium-Binding Proteins; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p21; DNA-Binding Proteins; ErbB Receptors; Fatal Outcome; Female; Gingival Neoplasms; Hepatocyte Growth Factor; Humans; Leiomyosarcoma; Middle Aged; Neoplasm Proteins; Platelet Endothelial Cell Adhesion Molecule-1; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Receptor, ErbB-2; Receptors, Cell Surface; Retinoblastoma Protein; Ribonuclease, Pancreatic; Serpins; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Uterine Neoplasms; von Willebrand Factor

Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process.. We determined ANG and MMP-2 in the placental tissues of 26 patients who had a benign mole (BM), 12 patients with gestational trophoblast neoplasia (GTN) (1 invasive hydatidiform mole, 10 choriocarcinomas, and 1 placental-site trophoblastic tumor), and 28 normal chorionic villi (NCV) subjects using immunohistochemistry staining. We obtained the serum samples from 20 patients with GTDs and 20 early pregnant women and evaluated them by the enzyme linked immunosorbent assay.. ANG expression in GTN (66.7%) and BM (100%) samples were both significantly higher (strong/intermediate staining) than in NCV (60.7%) samples (P < .001). Similarly, the immunoreactivities of MMP-2 in the GTN (66.7%) and BM (80.8%) samples were significantly elevated compared to that of the NCV (57.1%) samples (P < .001). The levels of ANG and MMP-2 in the maternal serum of the GTN group were both significantly higher than those of the control group (P < .001). ANG and MMP-2 expressions were associated with gestation age, clinical stage, and FIGO stage. A positive correlation between ANG and MMP-2 expression was observed (rs = 0.725; P < .01).. ANG and MMP-2 levels were significantly elevated in the placental tissues and maternal serum from patients with GTDs. Further studies with more patients may clarify the vascular abnormalities in GTDs and determine potential biomarkers in the differential diagnosis of GTDs.

Topics: Biomarkers; Diagnosis, Differential; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Matrix Metalloproteinase 2; Placenta; Pregnancy; Ribonuclease, Pancreatic; Uterine Neoplasms

The aim of this study was to evaluate the diagnostic and prognostic values of serum angiogenin concentration in cases with gestational trophoblastic diseases (GTDs). Seventy-two patients with GTDs and 20 first trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTDs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar gestational trophoblastic tumors of high risk (PMHR), 16 low-risk choriocarcinoma, and 14 high-risk choriocarcinoma. Before treatment, a blood sample from each case was assayed for human chorionic gonadotrophin , subunit (hCGb) by radioimmunoassay and angiogenin by enzyme immunoassay. Follow-up hCGb and angiogenin assays were carried out for 1 year after treatment. Pretreatment of abnormal values of serum angiogenin (> 711 ng/ml, upper 95% confidence interval of controls) was encountered in 100% of PMHR cases compared to no single case of HMSR. Serum angiogenin levels in low- and high-risk cases with choriocarcinoma were significantly higher than in controls. Abnormal high values were encountered in 25% and 86% of cases, respectively. None of the low-risk cases exceeded 920 ng/ml, while 72% of high-risk cases exceeded this value. Serial angiogenin assays were correlated with disease progression and were positively correlated with serum hCGb (r = 0.75, p < 0.01). In conclusion, serum angiogenin may be a valuable marker of differential diagnosis of GTDs and its serial measurements are suggestive of remission and effective therapeutic intervention or disease progression.

Topics: Adolescent; Adult; Biomarkers, Tumor; Case-Control Studies; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Disease Progression; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Pregnancy; Pregnancy Trimester, First; Prognosis; Ribonuclease, Pancreatic; Risk Factors; Uterine Neoplasms