S100 expression in dendritic cells is inversely correlated with tumor grade in endometrial carcinoma

OBJECTIVE: The aim of this study was to determine the expression of S100 positive dendritic cells (DCs) and the relationship with clinicopathologic factors in endometrial carcinoma. METHODS: Samples were collected from 89 patients with endometrial endometrioid adenocarcinoma treated in Pusan National University Hospital from 2004 to 2011. Normal endometrial tissues were obtained from 30 hysterectomized women with benign adnexal masses and served as controls. Paraffin-embedded sections were immunohistochemically stained for S100 was performed, and the number of positive DCs was counted. The relationship of these cells to the stage, histological grade, myometrial invasion, and lymph node metastasis was analyzed. RESULTS: The proportion of S100-positive DCs in the endometrial endometrioid adenocarcinoma was 31.5% (28/89), which was significantly higher (P<0.05) than in the control group. The proportion of S100-positive DC expression was negatively correlated with the histologic grade, but was not associated with the stage, myometrial invasion, or lymph node metastasis. CONCLUSION: High DC density was inversely correlated with histologic grade in endometrial carcinoma. Tumor-infiltrating S100+ DCs may be used as pathologic marker in endometrial carcinoma.

Comparison of the Usefulness of four Risk-of-Malignancy Indices using Ultrasonography in Ovarian masses

PURPOSE: The aim of this study was to evaluate the usefulness of four Risk-of-Malignancy Indices (RMI) in women with ovarian masses. MATERIALS AND METHODS: Between January 2007 and December 2008, 344 women who visited our hospital for surgical exploration due to an ovarian mass were enrolled in this study. Each RMI was based on the combination of menopausal status, ultrasound findings of ovarian masses, and absolute level of serum CA-125. A cutoff level of 200 was chosen as the threshold for determining between malignant and benign ovarian masses in RMI 1, RMI 2, and RMI 3. A cutoff level of 450 was chosen as the threshold in RMI 4. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: The combination of four malignancy indices is more accurate than menopausal status, ultrasound findings, and serum CA-125 alone, respectively for determining whether a mass is benign or malignant. RMI 1 and RMI 4 were found to be better than RMI 2 and RMI 3. RMI 4 was the most reliable test among them. The relationship between RMI 1 and RMI 4 was not statistically significant. With the cutoff level for RMI 4 at 450, the corresponding, sensitivity, specificity, positive predictive value, and negative predictive value were 72.1%, 88.0%, 56.4%, 93.9%, respectively. CONCLUSION: All four RMI were reliable tests for determining whether ovarian masses are malignant or benign, and RMI 4 was the most reliable index among them.

MyD88 expression and anti-apoptotic signals of paclitaxel in epithelial ovarian cancer cells / 대한산부인과학회지

OBJECTIVE: The objectives of this study was to evaluate the correlation between myeloid differentiation protein 88 (MyD88) expression and paclitaxel effects on epithelial ovarian cancer cells and to evaluate whether paclitaxel had anti-apoptotic signals. METHODS: Epithelial ovarian cancer cells isolated from ascites and established cell lines were treated with increasing concentrations of paclitaxel (0.2 to 20 microM) for 24 and 48 hours and cell viability was determined using the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. Nuclear factor-kappaB (NF-kappaB) activity was determined using a Luciferase reporter system. Levels of phospho-extracellular signal-regulated kinase (p-ERK) were measured by Western blot analysis. RESULTS: A strong signal for MyD88 expression was observed in R182, 01-19b and SKOV3 cells (MyD88-positive). A2780, R454 and 01-28 cells showed low levels of MyD88 (MyD88-negative). Paclitaxel effectively decreased cell viability in MyD88-negative A2780, R454, 01-28 cells after 24 and 48 hours (57%, 49%, 42% and 35%, 28%, 29%, respectively). MyD88-positive cells were resistant to paclitaxel. There was a significant increase in caspase-3/7 activity following paclitaxel treatment in MyD88-negative cells. No significant change in caspase-3/7 activity was detected in MyD88-positive cells. Paclitaxel induced NF-kappaB activation and enhanced the secretion of interleukin-6 (IL-6) and IL-8 in a dose dependent manner and induced ERK phosphorylation on MyD88-positive cells. CONCLUSION: Paclitaxel treatment for MyD88-positive ovarian cancer could have detrimental effects due to the paclitaxel-induced enhancement of NF-kappaB, ERK activities and pro-inflammatory cytokine production, which promote chemoresistance and tumor progression.

Comparison of pregnancy and implantation rates in fresh embryo transfer (ET) and frozen-thawed ET cycles in infertile women with polycystic ovarian syndrome / 대한산부인과학회지

OBJECTIVE: Aim of this study is to evaluate the pregnancy and implantation rates in fresh-embryo transfer (ET) and frozen-thawed ET cycles in women with polycystic ovarian syndrome (PCOS). METHODS: PCOS was diagnosed by the Rotterdam criteria. In 4 cases of 72 stimulation cycles, ET was not conducted due to severe ovarian hyperstimulation syndrome (OHSS). Sixty eight cycles of fresh-ET and 40 cycles of frozen-thawed ET were included in this retrospective study. Age, gravidity, body mass index, infertility duration were compared between two groups. Number of embryos transferred, implantation rate, clinical pregnancy rate and multiple pregnancy rate were compared between two groups by using chi-square test and student's t-test. RESULTS: Number of embryos transferred showed significant difference between two groups. Fresh-ET group was 4.7 and frozen-thawed ET group was 2.8 (P<0.001). However, overall clinical outcomes with fresh-ET and frozen-thawed ET cycles were similar. Implantation rates were 8.3% vs 11.5%, clinical pregnancy rates were 27.9% vs 25.0% and multiple pregnancy rates were 36.8% vs 20.0%. CONCLUSION: Although more number of embryos were transferred in fresh-ET cycles, the clinical outcomes were similar between fresh-ET and frozen-thawed ET cycles. It may be due to decreased uterine receptivity in fresh-ET cycles. Frozen-thawed ET may be used as alternative plan for cases of severe OHSS and decreased uterine receptivity expected.

Anti-proliferative effect in epithelial ovarian cancer cells by MEK Inhibitor AZD6244 / 대한산부인과학회지

OBJECTIVE: The objectives of this study were to determine the efficacy of AZD6244, a potent, selective MEK inhibitor, in epithelial ovarian cancer (EOC) cells and to determine the enhanced cell death by combined treatment of paclitaxel and AZD6244. METHODS: EOC cells were treated with tenfold dilutions of AZD6244 (0.1 to 10 micrometer) for 24, 48 and 72 hours. Cell viability was determined by the CellTiter 96 AQueous One Solution Cell Proliferation Assay. The apoptotic cascade was assessed by Caspase-Glo assays. ERK activation was evaluated by Western blot analyses. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. RESULTS: In vitro cell viability showed that ovarian cancer cells with high p-ERK activities (A2780, R454, 01-28) exhibited significant growth inhibition. Cells with low p-ERK activities (R182, CP70), however, were resistant to AZD6244. Caspase-3 was not activated during AZD6244-induced growth inhibition. AZD6244 significantly inhibited p-ERK1/2 in both cell types regardless of constitutive levels of p-ERK. Proinflammatory cytokines including IL-6, IL-8, MCP-1 and GM-CSF were significantly decreased. Paclitaxel activated the p-ERK levels in paclitaxel-resistant R182 cells with low basal p-ERK level. MEK inhibition by AZD6244 enhanced paclitaxel-induced apoptosis significantly in R182 cells. CONCLUSION: These results demonstrate that AZD6244 has a potent growth inhibitory effect in ovarian cancer cells with high p-ERK activities. In addition, targeted inhibition of the extracellular signal-regulated kinase pathway with AZD6244 can enhance the anti-tumor efficacy of the cytotoxic paclitaxel.

A case of Gliomatosis Peritonei after 10 years following Operation of Immature Teratoma of the Ovary / 부인종양

Gliomatosis peritonei, the implantation of neuroglial tissue upon the peritoneal surface, is a rare event most often associated with solid or immature teratoma of the ovary in young girls. The majority of cases occur in association with teratomas containing immature element. However malignant transformation of the glial tissue has been reported. Here we experienced a case of mature glial implants presenting in an 27-year-old female, 10 years after initial diagnosis and removal of an ovarian immature teratoma, and report this case with brief review of literatures.

Basal and Down-regulated Serum LH Levels as a Prognostic Indicator of Ovarian Response to Controlled Ovarian Hyperstimulation / 대한산부인과학회잡지

OBJECTIVE: The effect of basal day 3 luteinizing hormone (LH) and pituitary desensitized day 3 LH level on ovarian response to controlled ovarian hyperstimulation were investigated. METHODS: From January 1999 to December 2001, 445 cycles for in vitro fertilization and embryo transfer (IVF-ET) were allocated to this study. Controlled ovarian hyperstimulation (COH) was performed using long protocol of gonadotropin-releasing hormone agonist (GnRHa). All patients included in this study had blood samples drawn on cycle day 3 prior to COH and cycle day 3 after pituitary desensitization with GnRHa for measurement of FSH and LH. Infertile women were younger than 43 years old, and had normal menstrual cycle, normal day 3 FSH and LH level (<10 mIU/ml), infertility factor caused by tubal factor, mild endometriosis, unexplained infertility or mild male subfertility. The result of COH and IVF-ET were compared between low LH group and high LH group according to the level of basal LH (3 mIU/ml) and down-regulated LH (1 mIU/ml). RESULTS: The low LH groups were significantly higher FSH:LH ratio, higher dose of exogenous gonadotropin for pituitary desensitization, longer duration of gonadotropin administration. The peak estradiol, number of oocytes retrieved, number of MII oocyte, mean cumulative embryo score (MCES) were significantly lower in the low LH group than the high LH group. There were not significantly differentiation in the duration of pituitary desensitization, fertilization rate and the number of transferred embryos. The clinical pregnancy rate per cycle was not correlated with the value of basal LH concentration, but correlated with the value of down-regulated LH concentration. CONCLUSION: The lower LH activity (basal LH <3 mIU/ml, down-regulated LH <1 mIU/ml) is significantly associated with reduced ovarian response in controlled ovarian hyperstimulation after desensitization with GnRHa. These results suggest that down-regulated LH level 1 mIU/ml may be a useful predictor of the clinical pregnancy rate per cycle after controlled ovarian hyperstimulation.