Hyo Sook Bae

Detection of Microrna as Novel Biomarkers of Epithelial Ovarian Cancer From the Serum of Ovarian Cancer Patient

Objective MicroRNA (miRNA) is an abundant class of small noncoding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of serum-derived miRNAs of ovarian cancer based on a comparative study using a miRNA microarray of serum, tissue, and ascites. Methods From 2 ovarian cancer patients and a healthy control, total RNA was isolated from their serum, tissue, and ascites, respectively, and analyzed by a microarray. Under the comparative study of each miRNA microarray, we sorted out several miRNAs showing a consistent regulation tendency throughout all 3 specimens and the greatest range of alteration in serum as potential biomarkers. The availability of biomarkers was confirmed by qRT-PCR of 18 patients and 12 controls. Results Out of 2222 kinds of total miRNAs that were identified in the microarray analysis, 95 miRNAs were down-regulated and 88 miRNAs were up-regulated, in the serum, tissue, and ascites of cancer patients. Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR. Conclusions Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer. Also, serum miRNAs is a promising and useful tool for discriminating between controls and patients with serous ovarian cancer.

Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis

BackgroundStudies on the association between obesity and ovarian cancer survival have had conflicting results. We reviewed and quantitatively summarized the existing evidence, exploring potentially important sources of variability, such as the timing of body mass index (BMI) assessment, BMI cut points, references used in multivariate analysis, and ovarian cancer stage.MethodsEligible studies were searched using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials, relevant bibliographies were manually reviewed for additional studies. Adjusted hazard ratios (HRs) from individual studies were pooled using a random effects model.Results17 cohort studies of 929 screened articles were included in the final analysis. Obesity in early adulthood and obesity 5 years before ovarian cancer diagnosis were associated with poor patient survival (early adulthood: pooled HR 1.67; 95% CI 1.29-2.16; 5 years prediagnosis: pooled HR 1.35; 95% CI 1.03-1.76). However, the results for obesity at diagnosis depended on whether BMI was analyzed as a categorical or continuous variable. Analysis of obesity with BMI as a categorical variable did not affect ovarian cancer prognosis (pooled HR 1.07; 95% CI 0.95-1.21); obesity with BMI as a continuous variable showed slightly poorer survival with each incremental increase in BMI (pooled HR 1.02; 95% CI 1.01-1.04).ConclusionsObesity 5 years before ovarian cancer diagnosis and obesity at a young age were associated with poor prognosis. The association between obesity at diagnosis and survival of ovarian cancer patients still remains equivocal. BMI at diagnosis cannot be a prognostic factor for the survival of ovarian cancer patients. Further well-designed studies are needed to elucidate the variety effect of obesity on the survival of ovarian cancer patients.

Should endometrial clear cell carcinoma be classified as type II endometrial carcinoma

Endometrial clear cell carcinomas (ECCCs) are considered to be Type II endometrial carcinomas, like uterine serous adenocarcinoma (SCA), and therefore aggressive clinical management is indicated. However, according to the limited clinical, immunohistochemical, and molecular data available in the literature, ECCCs show overlapping features of SCA and endometrioid adenocarcinomas. Therefore, questions regarding their designation as the Type II carcinomas have been raised. We performed immunohistochemical staining for hepatocyte nuclear factor-1&bgr; and napsin A for the histologic confirmation of clear cell carcinoma (CCC), and analyzed immunohistochemical findings for estrogen receptor, progesterone receptor, HER2/neu, p53, p16, ARID1A, PTEN, DNA mismatch-repair proteins along with other prognostic factors. We performed DNA sequencing for the K-RAS, BRAF, PIK3CA, and PTEN genes for 16 pure CCCs. No patients with pure CCC experienced recurrent disease or died of the disease (0/16, 0%). ECCCs had SCA-like features with rare expression of estrogen receptor/progesterone receptor (18.8%/6.3%) and no K-RAS mutations, intermediate features regarding expressions of p53 (37.5%) and p16 (25%), and endometrioid adenocarcinoma-like features regarding losses of PTEN (81.3%), ARID1A (25%) and mismatch-repair protein (68.8%), expression of microsatellite instability-high (25%), HER2/neu (12.5%), and PIK3CA mutations (18.8%). Pure ECCC should not be regarded as Type II carcinoma, because it shares the immunohistochemical and molecular characteristics of Type I endometrioid adenocarcinoma and Type II SCA.

Evaluation of risk factors of vaginal cuff dehiscence after hysterectomy

Objective The purpose of this study was to evaluate risk factors of vaginal cuff dehiscence or evisceration according to the type of operation. Methods Medical records of 604 women who underwent hysterectomies at Korea University Anam Hospital between June 2007 and June 2011 were reviewed. They were allocated to six groups. The six types of hysterectomies included robotic hysterectomy (n = 7), robotic radical hysterectomy and node dissection (RRHND, n = 9), total laparoscopic hysterectomy (TLH, n = 274), laparoscopy assisted vaginal hysterectomy (LAVH, n = 238), laparoscopic radical hysterectomy and node dissection (n = 11), and abdominal radical hysterectomy (ARH, n = 63). The characteristics and outcomes of each groups were compared. Results There was no difference in the characteristics of patients between 6 groups. In total of 604 hysterectomies, 3 evisceration (0.49%) and 21 dehiscences (3.47%) occurred. Evisceration were found in RRHND (1/9, 11.1%), TLH (1/276, 0.36%), and ARH (1/63, 1.56%). Dehiscences occurred in TLH (15/274, 5.42%), LAVH (4/238, 1.68%), and ARH (2/63, 3.17%). In 169 cases of TLH with intra-corporeal continuous suture, 1 evisceration and 4 dehiscences occurred, whereas 11 dehiscences occurred in 105 TLH cases with vaginal continuous locking suture (2.96% vs. 10.47%, P = 0.02). Conclusion The incidence of vaginal cuff dehiscenceand eviscerationwas significantly higher in TLH than LAVH. The intra-corporeal cuff suture was superior to the vaginal suture to prevent the vaginal cuff complications in TLH.

Candidates for Tumor Markers of Cervical Cancer Discovered by Proteomic Analysis

Cervical cancer is the second most common gynecological cancer among Korean women. While nationwide screening program has developed, the pathogenesis of cervical cancer is unknown. The aim of this study was to compare the protein expression profiles between cervical squamous carcinomas and normal cervical tissues in order to identify proteins that are related to the cancer. Three cervical cancer tissue samples and three normal cervical tissue samples were obtained and protein expression was compared and was identified in the samples with the use of matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 20 proteins that showed up-regulated expression in the cervical cancer tissue samples were selected and identified. Seven proteins were matched to allograft inflammatory factor 1 (AIF-1), actine-like protein 2 (ALP2), brain type fatty acid-binding protein (B-FABP), NCK adaptor protein 1 (NCK-1), islet cell autoantigen 1 (ICA69), cationic trypsinogen (PRSS1), and cyclin-dependent kinase 4 (CDK4), but the remaining 13 proteins were unidentifiable. After confirmation by RT-PCR, Western blotting and immunohistochemistry, we found that B-FABP, NCK-1, and CDK4 were related to the pathogenesis of cervical cancer. These proteins are suggested as candidates of new pathological tumor markers for cervical cancer.

Circulating endothelial progenitor cells in gynaecological cancer

Objectives To compare the frequency and absolute numbers of circulating endothelial progenitor cells (EPCs) in healthy control subjects and patients with gynaecological cancer, and to test the hypothesis that cancer treatment lowers EPC numbers. Methods Patients with cervical or ovarian cancer and healthy control subjects provided peripheral blood samples for the isolation of mononuclear cells. EPCs were identified by quadruple immunofluorescence staining and flow cytometry as CD45–/CD34+/CD133+/vascular endothelial growth factor receptor 2 (VEGFR2)+ cells. Results In total, 28 participants were enrolled. Circulating EPCs were present at higher frequencies (and in greater absolute numbers) in patients with cervical or ovarian cancer (n = 14) than in controls (n = 14). Concurrent chemoradiation therapy or surgery significantly reduced the frequency and number of EPCs in patients with gynaecological cancer, compared with pretreatment levels. Conclusions EPC levels decline throughout cancer treatment; their measurement may therefore be a useful surrogate marker to monitor treatment response.

The effect of body mass index on survival in advanced epithelial ovarian cancer

Controversy remains regarding the effect of obesity on the survival of patients with ovarian cancer in Asia. This study examined the impact of obesity on the survival outcomes in advanced epithelial ovarian cancer (EOC) using Asian body mass index (BMI) criteria. The medical records of patients undergoing surgery for advanced (stage III and IV) EOC were reviewed. Statistical analyses included ANOVA, chi-square test, Kaplan-Meier survival and Cox regression analysis. Among all 236 patients, there were no differences in overall survival according to BMI except in underweight patients. In a multivariate Cox analysis, surgical optimality and underweight status were independent and significant prognostic factors for survival (HR, 2.302; 95% CI, 1.326-3.995; P=0.003 and HR, 8.622; 95% CI, 1.871-39.737; P = 0.006, respectively). In the subgroup of serous histology and optimal surgery, overweight and obese I patients showed better survival than normal weight patients (P = 0.012). We found that underweight BMI and surgical optimality are independent risk factors for the survival of patients with advanced ovarian cancer. High BMI groups (overweight, obese I and II) are not associated with the survival of advanced EOC patient. However, in the subgroup of EOC patients with serous histology and after optimal operation, overweight and obese I group patients show better survival than the normal weight group patients. Graphical Abstract

Cancer of the supernumerary ovary in Mayer‑Rokitansty‑Küster‑Hauser Syndrome: A case report

Mayer-Rokitansty-Küster-Hauser (MRKH) syndrome is a Müllerian anomaly that presents with varying degrees of uterovaginal aplasia and is secondarily associated with cervicothoracic, auditory and skeletal anomalies. However, MRKH syndrome patients have normal and functional ovaries. A supernumerary ovary is an extremely rare form of an ectopic ovary and there are no reported cases of MRKH syndrome with cancer of the supernumerary ovary in the current literature. A 31-year-old female with a history of MRKH syndrome that was diagnosed 4 years previously presented with abdominal pain and a suspected malignant pelvic mass was identified. During the staging surgery, both ovaries were separated from the main mass, observed and removed. A third ovary was discovered in the pelvic mass and the diagnosis of primary ovarian cancer from the third ovary was confirmed by immunohistochemistry. We report the first known case of cancer of the supernumerary ovary in a patient with MRKH syndrome. Although both ovaries were confirmed to be normal in the patient with MRKH syndrome, we propose that an ovarian neoplasm should be considered in the diagnosis of a pelvic mass.

Endometrial mullerian adenosarcoma after toremifene treatment in breast cancer patients: a case report.

Toremifene is an anti-estrogen which has been shown to be effective in the treatment of breast cancer, and is thought to be a less uterotrophic agent than tamoxifen. The risk assessment concerning endometrial cancer has been inconclusive because of its rare use up to the mid-1990s. We report a case of an adenosarcoma, which is a very rare type of uterine malignancy, after toremifene treatment for 5 years in a breast cancer patient. After 1 year of toremifene use, the patient had a benign Mullerian adenofibroma. After an additional 4 years of toremifene treatment, the endometrial polypoid lesion was transformed into a Mullerian adenosarcoma. Although toremifene is a promising anti-estrogenic agent in the treatment of breast cancer patients, clinicians should not neglect the possibility of a uterine malignancy.

Uterine fibroid shrinkage after short-term use of selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

Objective The aim of this study was to evaluate the effect of short-term use of selective progesterone receptor modulator (SPRM) or gonadotropin-releasing hormone (GnRH) agonist on uterine fibroid shrinkage among Korean women. Methods This retrospective study involved 101 women with symptomatic uterine fibroids who received ulipristal acetate (SPRM, n=51) and leuprolide acetate (GnRH agonist, n=50) for 3 months between November 2013 and February 2015. The fibroid volume was measured both before and after treatment using ultrasonography, computed tomography, and magnetic resonance imaging. The outcomes were compared between the SPRM and GnRH agonist groups. Results The median rate of fibroid volume reduction after SPRM treatment was 12.4% (IQR −14.5% to 40.5%) which was significantly lower than the reduction rate observed after GnRH agonist treatment (median 34.9%, IQR 14.7% to 48.6%, P=0.004). 19 of 51 (37.3%) patients with SPRM treatment did not show any response of volume shrinkage, while 7 of 50 (14.0%) women with GnRH agonist showed no response (P=0.007). Conclusion Short-term SPRM treatment yields lower volume reduction than GnRH agonist treatment in Korean women with symptomatic fibroids. Further large-scale randomized trials are needed to confirm our findings.