High negative prediction for the Basel sarcoma score: Sonographic assessment of features suspicious of uterine sarcoma.

INTRODUCTION: In the management of uterine myomas, laparoscopic surgery with morcellation enables a minimal invasive procedure. Cases of unsuspected uterine sarcoma dissemination have been reported and led to regulative restrictions. To help to distinguish preoperatively myomas from sarcomas, we assessed the value of six sonographic criteria (Basel Sarcoma Score, BSS) in a prospective outpatient cohort of consecutive patients with uterine masses. MATERIAL AND METHODS: We prospectively evaluated all patients presenting with myoma-like masses planned for surgery with standardized ultrasound examination. BSS including the following criteria was investigated: rapid growth in past three months, high blood flow, atypical growth, irregular lining, central necrosis and oval solitary lesion. For each criterion, a score 0/1 was given. BSS (0-6) equals the sum of all given scores. Histological diagnosis was used as reference. RESULTS: Among 545 patients, 522 had the final diagnosis of myoma, 16 had peritoneal masses with sarcomatous components (PMSC), and seven had other malignancies. Median BSS for PMSC was 2.5 (range: 0-4) vs 0 for myomas (range: 0-3). The most common sonographic criteria leading to a false positive score in myomas were rapid growth in past three months and high blood flow. For the detection of sarcomatous masses with BSS threshold of >1, sensitivity was 93.8%, specificity 97.9%, and positive predictive value (PPV) and negative predictive value (NPV) were 57.7% and 99.8%, respectively (AUC 0.95). CONCLUSION: BSS can help distinguishing between myomas and sarcomatous masses, with high NPV. Caution is required when >1 criterion is present. As a simple tool, it could easily be integrated into routine myoma sonographic examination and help develop standardized assessment of uterine masses for better preoperative triage.

MELK expression in ovarian cancer correlates with poor outcome and its inhibition by OTSSP167 abrogates proliferation and viability of ovarian cancer cells.

OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis). RESULTS: Elevated MELK expression was correlated with histological grading (n=6 data sets, p<0.05) and progression-free survival (HR 5.73, p<0.01) in OC patients and elevated MELK expression in other cancers with disease-free survival (n=3495, HR 1.071, p<0.001). Inhibition or depletion of MELK reduced cell proliferation and anchorage-dependent and -independent growth in various OC cell lines through a G2/M cell cycle arrest, eventually resulting in apoptosis. OTSSP167 retained its cytotoxicity in Cisplatin- and Paclitaxel-resistant IGROV1 and TYK-nu OC cells and sensitized OVCAR8 cells to Carboplatin but not Paclitaxel. CONCLUSION: MELK inhibition by OTSSP167 may thus present a strategy to treat patients with aggressive, progressive, and recurrent ovarian cancer.

Improved Detection Rate of Ovarian Cancer Using a 2-Step Triage Model of the Risk of Malignancy Index and Expert Sonography in an Outpatient Screening Setting.

OBJECTIVE: Preoperative assessment of adnexal masses with ultrasound has been shown to be time-, cost-effective, and specific. When used in combination with the menopausal status and the tumor marker CA125, the risk of malignancy index (RMI) can be calculated, allowing appropriate preoperative triage of patients to a gynecologist or a gynecological oncologist. Moreover, it allows for accurate planning of the required surgical procedure (laparoscopy vs laparotomy). METHODS: A large general gynecologic ultrasonic database retrospectively identified 5218 patients for a 14-year period who presented to the outpatient clinic with an adnexal mass. Additional data (menopausal status, histology, CA125 values) were available in 1108 of these patients. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The results were then compared with previously published data from a large Australian gynecological cancer center (GCC, n = 204). RESULTS: With the use of an RMI cutoff of 200, malignant ovarian tumors were correctly triaged to a gynecologic oncologist in 123 of 172 cases, leading to a sensitivity of 72% and specificity of 92% in our general outpatient clinic population compared with a sensitivity of 84% and a specificity of 77% in the GCC high-risk population. The negative predictive value was 95% compared with only 85% in the GCC cohort. We hypothesize that improvement of the overall detection rate of malignancy could be improved from 72% to 85% using a 2-step model, referring patients with an ultrasonic score of 3 to an experienced sonographer who uses pattern recognition. CONCLUSIONS: The RMI is an easy and reliable tool for the accurate triage of adnexal masses. Its value is higher in an unselected gynecological outpatient setting. Our proposed 2-step model including expert pattern recognition could influence particularly the detection rate in borderline and early-stage ovarian cancers and overcome the limitations of the tumor marker CA125.

Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion.

AIM: In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic and therapeutic targets. Here we investigated the role of two Wnt receptor tyrosine kinases (RTKs), ROR1 and ROR2, and their putative ligand, Wnt5a, in ovarian cancer. METHODS: Immunohistochemistry for ROR2 was performed in a large patient cohort, including benign controls, borderline tumours and epithelial ovarian cancer. In addition, siRNA was used to silence ROR1, ROR2 and Wnt5a individually, and together, in two ovarian cancer cell lines, and the effects on cell proliferation, adhesion, migration and invasion were measured. RESULTS: ROR2 expression is significantly increased in ovarian cancer patients compared to patients with benign disease. In vitro assays showed that silencing either receptor inhibits ovarian cancer cell migration and invasion, and concurrently silencing both receptors has an even stronger inhibitory effect on proliferation, migration and invasion. CONCLUSIONS: ROR2 expression is increased in epithelial ovarian cancer, and silencing ROR2 and its sister receptor ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade through an extracellular matrix.