Serum Copper and Zinc Levels in Patients with Endometrial Cancer.

The aim of the present study was to evaluate serum concentrations of copper (Cu) and zinc (Zn), in relation with metabolic profile and clinicopathologic features of patients with endometrial cancer. A total of 47 women with endometrial cancer and 45 controls were eligible for the study. Clinicopathologic features and metabolic profile as well as serum copper and zinc levels were evaluated in each subject. Patients with endometrial cancer (Cu mean 3.72 ± 2.15 mg/L, median 3.54 [0.41-9.16] mg/L and Zn mean 1.83 ± 0.71 mg/L, median 1.77 [0.71-4.02] mg/L) exhibited lower Cu and Zn levels than those of controls (Cu mean 6.06 ± 1.79 mg/L, median 6.32 [2.95-9.05] mg/L and Zn mean 2.48 ± 0.89 mg/L, median 2.23 [1.23-4.54] mg/L) (p < 0.001). Cu/Zn ratio was also higher (0.85 ± 1.96 vs. 2.57 ± 0.73) in controls as compared with patients with endometrial cancer. While Cu levels showed no significant correlation with age, body mass index, gravidity, and parity, a positive correlation was found between Zn levels and parity. When cancer patients were evaluated on their own, both Cu and Zn levels showed positive correlation with age. Additionally, the cancer patients with myometrial invasion > 1/2 exhibited lower Cu levels compared with the cancer patients with myometrial invasion < 1/2. The data of the present study suggested that women with endometrial cancer are characterized by altered serum Cu and Zn levels as compared with controls. Imbalance of these trace element levels might be associated with endometrial cancer among Turkish patients.

Analysis of TP53 gene in uterine myomas: No mutations but P72R polymorphism is associated with myoma development.

AIM: The aim of the present study was to investigate the familial and somatic mutations as well as polymorphisms of TP53 gene in patients with uterine leiomyoma. METHODS: The study included 35 women with histologically diagnosed as uterine leiomyomas at the Gynecology Department of Adnan Menderes University Faculty of Medicine. Tissue and blood samples were analyzed for mutations and polymorphisms of TP53 gene by next generation sequencing (Miseq-Illumina). Acquired data was compared with the normal data in Ensembl database. Data from 1000 genome project and data from exome sequencing analyses in Intergen Genetic Diagnosis Center (Ankara) were used as controls for polymorphism analyses. RESULTS: There were no mutations in tissue and blood samples. However, when the polymorphisms were evaluated, a significant difference was found in NM_000546.5(TP53):c.215C > G (p.Pro72Arg) polymorphism between the study and control groups. The results indicated that P72R/P72R genotype increased the risk of leiomyoma development by 6.3 fold (95% confidence interval [CI]: 2.880-13.793). There was a negative correlation between P72R/WT genotype and leiomyoma development (OR = 0.261, 95% CI: 0.114-0.596). P72R/P72R genotype was statistically higher in the patients with leiomyoma compared with the controls and 1000 genomes from Asian, European and World populations. CONCLUSION: The results of the present study suggested that P72R/P72R genotype may be associated with development of uterine leiomyoma in the Turkish population in the Western part of the country.

The effects of resveratrol on ovarian hyperstimulation syndrome in a rat model.

OBJECTIVE: The aim of the present study was to investigate effects of resveratrol (RSV) over ovarian hyperstimulation syndrome (OHSS) in rat model. MATERIALS AND METHODS: 24 female Wistar rats (22 days old) were divided into four groups. Group 1 (control group; n = 6) received 0.1 ml intraperitoneal (IP) saline from days 22-26; group 2 (mild-stimulated group; n = 6) received 10 IU pregnant mare serum gonadotropin (PMSG) on day 24 and 10 IU of hCG 48 h later (day 26); group 3 (OHSS group; n = 6) was given 10 IU of PMSG for 4 consecutive days from day 22 and 30 IU hCG on the fifth day to induce OHSS; group 4 (OHSS + RSV group; n = 6) was treated the same as group 3, but received 60 mg/kg RSV 2 h before PMSG injection for 4 consecutive days and 2 h before the hCG injection on the fifth day. RESULTS: Weight gain was highest in the OHSS group. Ovarian weights were lower in the treatment group than OHSS group. Peritoneal fluid VEGF levels were lower for RSV group compared to group 2 and 3. Total VEGF immunoreactivity was higher in OHSS group than group 1, 2 and 4. CONCLUSION: These results indicate that RSV is beneficial for prevention of OHSS by reducing the increases in body and ovarian weight and VEGF activity. These effects may be mediated by anti-inflammatory, anti-oxidant and anti-angiogenic capacity of RSV.

Elevated PAPP-A levels in lean patients with polycystic ovary syndrome.

OBJECTIVES: This study aimed to evaluate the serum concentrations of PAPP-A (pregnancy associated placental protein-A), a biomarker which is associated with cardiovascular disease, in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 62 women with PCOS, and 68 age and body mass index (BMI) matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as PAPP-A levels were assessed in each subject. RESULTS: Women with PCOS and controls yielded similar median serum levels of PAPP-A (1.7 ng/ml versus 1.8 ng/ml, respectively, p = 0.328). However, when patients were compared based on BMI; subgroup analyses found that among women with BMI<27 kg/m2, patients with PCOS exhibited higher PAPP-A levels than controls (2.1 ng/ml versus 1.8 ng/ml, respectively, p = 0.018). When women with PCOS were evaluated in their own based on BMI, lean PCOS women showed higher levels of PAPP-A (2.1 ng/ml versus 1.5 ng/ml, p = 0.002). PAPP-A levels were negatively correlated with age (p = 0.031, r = -0.189), BMI (p = 0.002, r = -0.265) and triglyceride levels (p < 0.001, r = -0.3). CONCLUSION: The data of the present study suggested that PAPP-A might be a clinical indicator in PCOS, in which the risks of metabolic syndrome and cardiovascular event are increased. Especially a group of young patients with BMI <27 kg/m2 might benefit from the cardiovascular risk evaluation using PAPP-A, supplying prognostic information for high risk in the development of cardiovascular disease.

Apelin levels are higher in obese patients with endometrial cancer.

AIM: The aim of the present study was to evaluate serum concentrations of apelin, a newly discovered adipocytokine, in relation with tumor markers, metabolic profile and clinicopathologic features of patients with endometrial cancer. MATERIAL AND METHODS: A total of 46 women with endometrial cancer and 44 controls were eligible for the study. Clinicopathologic features and metabolic profile as well as apelin-36 levels were evaluated in each subject. RESULTS: Women with endometrial cancer exhibited higher serum concentrations of apelin levels than controls (215.1 ± 59.8 pg/mL vs 177.3 ± 55.2 pg/mL, P = 0.002). Apelin levels were significantly correlated positively with body mass index, fasting insulin levels and homeostasis model assessment index (P < 0.05). When patients were further divided into obese (body mass index ≥ 30) and non-obese women, apelin levels remained higher in women with endometrial cancer in the obese group (P = 0.006, 243.5 ± 49.2 pg/mL vs 200.5 ± 52.7 pg/mL, respectively); whereas these levels were similar in the non-obese group (P = 0.879, 161.9 ± 37.5 pg/mL vs 159.6 ± 51.3, respectively). After adjustment for all possible confounding factors, age, apelin levels > 160 pg/mL, and diabetes mellitus were found to be associated with risk of endometrial cancer. CONCLUSION: The data of the present study suggest that higher levels of circulating apelin are associated with an increased risk of developing endometrial cancer in obese women.

Effect of luteal phase support after ovulation induction and intrauterine insemination.

OBJECTIVE: This study aimed to evaluate the effect of luteal phase support on clinical pregnancy and live birth rates after ovulation induction and intrauterine insemination (IUI). METHODS: 579 cycles from 2010 to 2013 were retrospectively evaluated. Ovarian stimulation was performed with gonadotropins, and rHCG was used for ovulation triggering. All patients received IUI. 451 cycles were supported by receiving vaginal micronized progesterone capsules (142 cycles) or vaginal progesterone gel (309 cycles) whereas 128 cycles were not supported. RESULTS: Clinical pregnancy (20.6 versus 9.4%; p = 0.004) and live birth rates (14 versus 7%; p = 0.036) were higher for supported group than for unsupported group. Progesterone gel and micronized progesterone subgroups achieved similar clinical pregnancy and live birth rates (21.4 versus 19%, p = 0.567 and 14.2 versus 13.4%, p = 0.807; respectively). CONCLUSIONS: Luteal phase support improved the success of IUI cycles affecting both clinical pregnancy and live birth rates when gonadotropins were used for ovulation induction. The use of vaginal progesterone gel or micronized progesterone significantly improves clinical pregnancy rates. The live birth rates were higher in the progesterone gel group, but were similar in the micronized progesterone group compared to the unsupported group.

Vascular endothelial growth factor +405 C/G polymorphism is highly associated with an increased risk of endometriosis in Turkish women.

OBJECTIVE: Endometriosis is a chronic gynecological disease characterized by the growth of hormonally responsive, endometrial tissue outside the uterine cavity. The present study aims to analyze two vascular endothelial growth factor (VEGF) polymorphisms (-460 C/T and +405 C/G) in Turkish women with and without endometriosis. STUDY DESIGN: A case-control study was undertaken at the Infertility Department of Zekai Tahir Burak Women's Health Care Education and Research Hospital. The single nucleotide polymorphisms, -460 C/T and +405 C/G, in the 5'-untranslated region of the VEGF gene were tested in 98 affected women and 94 women with no laparoscopic evidence of disease. Endometriosis was also confirmed histologically. Following genomic extraction of genomic DNA, genotyping of the -460 C/T and +405 C/G polymorphisms of the VEGF gene were performed by polymerase chain reaction and restriction fragment length polymorphism assay. Nominal data were evaluated by Pearson Chi-square or Fisher's Exact test, where applicable. Odds ratios and 95% confidence intervals were also calculated. A P value less than 0.05 was considered statistically significant. RESULTS: Demographic data were similar among groups. The genotype and allele frequencies of the -460 C/T polymorphism did not differ significantly between cases and controls. In contrast, the genotype (P < 0.001) and allele frequencies (P < 0.001) of +405 C/G polymorphism showed a significant difference between cases and controls. Regardless of the early or advanced stage, women with endometriosis showed a higher incidence of the +405 GC genotype and +405G allele when compared with the controls. CONCLUSIONS: These data suggest that VEGF +405 GC genotype and +405G allele may be associated with the risk of developing early and advanced stage endometriosis in the Turkish population.

Malign mural nodules associated with serous ovarian tumor of borderline malignancy: a case report and literature review.

BACKGROUND: Cystic tumors of ovary, whether benign, borderline, or malignant may be associated with mural nodule of various types, including sarcomas, sarcoma-like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous borderline ovarian tumor with mural nodules of mixed type are very rare. CASE: A 54-year-old woman referred with abdominal swelling. Imaging studies revealed a huge mass localized in pelvis and lower abdomen and grade 1-2 left renal hydronephrosis. Preoperative Ca-125 was 798 U/ml. In exploratory laparotomy there was a 16 cm mass adherent to lateral abdominal wall and intestines. Adhesiolysis and de-bulking surgery were performed including bilateral pelvic, para-aortic lymphadenectomy, appendectomy and omentectomy. Left ureter was found to be dilated because of the infiltration of distal part by the tumor, so distal ureteral resection and neoureterocystostomy were performed. Final pathology revealed borderline serous ovarian tumor with mural nodules which were consisted of SLMNs, multiple and sharply demarcated from the adjacent tumor, and sarcomatous nodules showing infiltrative appearance in metastatic regions. Mural nodules showed a positive reaction for vimentin and SMA but were negative for cytokeratin and also necrosis, hemorrhage, and 10-15 mitoses in 10 high power fields were noted. She had postoperative chemotherapy and follow-up is going on without metastases in her first year. CONCLUSION: The existence of sarcomatous nodules combined with the SLMN necessitates a careful histologic analysis for treatment and the determination of prognosis. However, too few cases of mixed type mural nodules have been published to warrant a conclusion regarding their prognosis.