Assessing the Phenotype of a Homologous Recombination Deficiency Using High Resolution Array-Based Comparative Genome Hybridization in Ovarian Cancer.

Ovarian cancer (OC) cells with homologous recombination deficiency (HRD) accumulate genomic scars (LST, TAI, and LOH) over a value of 42 in sum. PARP inhibitors can treat OC with HRD. The detection of HRD can be done directly by imaging these genomic scars, or indirectly by detecting mutations in the genes involved in HR. We show that HRD detection is also possible using high-resolution aCGH. A total of 30 OCs were analyzed retrospectively with high-resolution arrays as a test set and 19 OCs prospectively as a validation set. Mutation analysis was performed by HBOC TruRisk V2 panel to detect HR-relevant mutations. CNVs were clustered with respect to the involved HR genes versus the OC cases. In prospective validation, the HRD status determined by aCGH was compared with external HRD assessments. Two BRCA mutation carriers did not have HRD. OC could approximately differentiate into two groups with characteristic CNV patterns with different survival rates. Mutation frequencies have a linear regression on the HRD score. Mutations in individual HR-relevant genes do not always indicate HRD. This may depend on the mutation frequency in tumor cells. The aCGH shows the genomic scars of an HRD inexpensively and directly.

Notch1 Affects Chemo-resistance Through Regulating Epithelial-Mesenchymal Transition (EMT) in Epithelial Ovarian cancer cells.

Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, chemo-resistance is the main cause for treatment failure. Our previous studies have found that SKOV3 could promote immune escape and tumor progression via Notch1 pathway. Therefore, Notch1 is suspected to be involved in chemo-resistance. The current study is to investigate the possible mechanisms of platinum-resistance in epithelial ovarian cancer mediated by Notch1. Methods: The expressions of Notch1, Snail, MMP-2, N-cadherin, Vimentin and E-cadherin were detected by Western-blot. A stable high expression or low expression of Notch1 in ovarian cancer cells was established by using lentiviral gene engineering. The cell migration and invasion ability were observed by scratch test and transwell test. Cell apoptosis rate and cell cycle were analyzed by flow cytometry. Results: The expression levels of Notch1, Snail, MMP-2, N-cadherin and Vimentin in ovarian cancer were high, while the expression levels of E-cadherin were low.Notch1 promoted the expression of Snail, vimentin, N-cadherin and MMP2 protein, but inhibiting the expression of E-cadherin, promoting cell migration and invasion. Notch1 affected apoptosis of cells through Epithelial-Mesenchymal Transition (EMT), increasing the proportion of cells in S phase and G2 phase, thus affecting drug resistance. Conclusion: Notch1 affects EOC cells chemo-resistance by regulating EMT. This may provide a new target for the treatment of ovarian cancer.

Clinical Predictors of Recurrence and Prognostic Value of Lymph Node Involvement in the Serous Borderline Ovarian Tumor.

AIM: This study was aimed to evaluate the risk factors of recurrence and the value of nodal involvement in patients with serous borderline ovarian tumors (SBOT). METHODS: Two hundred twenty-five patients who underwent surgery and were diagnosed with SBOT were retrospectively studied. Univariate and multivariate analyses were used to assess the risk factors for recurrence. Patients' clinical pathologic characteristics were compared between the patients who presented lymph node involvement and those who did not. The significant values of lymph condition influencing 5-year disease-free survival were also evaluated by statistical analysis. RESULTS: Both univariate and multivariate analyses showed that risk factors for recurrence were micropapillary (P = 0.021), fertility-preserving surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients on whom lymphadenectomy was performed, 17 cases showed lymph node positive, whereas the remaining 95 patients did not. Significant differences in terms of lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5-year disease-free survival revealed that there were no significant differences either between groups of lymphatic node involved or not (P = 0.778) and groups of removed nodes whether more than 10 or not (P = 0.549). CONCLUSIONS: Micropapillary, fertility-preserving, and laparoscopic approach were factors significantly affecting the recurrence of SBOT by both univariate and multivariate analysis. Lymph node metastasis did not seem to be correlated to a worse prognosis of SBOT.

Inhibition of Notch 1 receptor influenced the differentiation of Lin-CD45RA-dendritic cell precursors within ovarian carcinoma microenvironment.

BACKGROUND: Previous evidence suggested that the differentiation of Lin-CD45RA-DC precursors were prior to plasmcytoid dendritic cells (pDCs) than myeloid dendritic cells (mDCs) within ovarian cancer microenvironment. However, the mechanism is still unclear. Therefore, we investigated the function of Notch 1 signal pathway in the differentiation of Lin-CD45RA-DC precursors. METHODS: The CD34+ hematopoietic stem cells were extracted from umbilical cord blood in term parturition, and Lin-CD45RA-DC precusors were separated and induced mature. Expression of Notch1 receptor and ligands in Lin-CD45RA-DC precusors was detected by Real-time PCR and was down-regulated by shRNA or γ-secretase inhibitor (GSI). Flow cytometry was used to analyze the subset of DCs with or without SKOV3 culture supernatants. IL-12 level was detected by ELISA. RESULTS: Expression of Notch1 receptors and ligands were detected in Lin-CD45RA-DC precursor cells. The Notch1 mRNA in Lin-CD45RA-DC precursors can be down-regulated by shRNA-Notch1 lentivirus transfection and GSI. ShRNA mediated Notch 1 knock-down significantly differentiated less plasmcytoid dendritic cells (pDCs), but generated more myeloid dendritic cells (mDCs), and this would not be influenced by the supernatant of the ovarian carcinoma cell line. GSI had the same effect in the differentiation of pDC. The secretion of IL-12 significantly increased after Notch1 knock-down with or without SKOV3 culture supernatants. CONCLUSIONS: Notch1 is an important signaling pathway in the differentiation of Lin-CD45RA-DC precursor cells to plasmcytoid dendritic cells (pDCs). And this would not be affected by the supernatant of the ovarian carcinoma cell line.

Long-term outcome of patients with persistent low-level elevation of human chorionic gonadotrophin.

AIM: The aim of this study was to investigate a series of patients with sustained low-level elevated human chorionic gonadotrophin (hCG) and explore the management of these patients. METHODS: A total of 47 patients with persistent low levels of hCG were selected for analysis between January 2002 and January 2014 at the Women's Hospital of Zhejiang University, Hangzhou, China. Data were retrospectively reviewed for patient characteristics, therapeutic strategies, and follow-ups. We compared the characteristics of patients who were and were not eventually considered to have malignancies. RESULTS: Among the 47 patients, 17 with persistent low-level elevated hCG and no detectable lesions were considered to have no active malignancy. Fifteen of the 17 patients had hCG levels that returned to normal range by the end of follow-up, while the remaining two did not. The other 30 patients were eventually diagnosed as having active malignancies due to detected lesions or increasing elevation of hCG. A large proportion of these patients were diagnosed with placental site trophoblastic tumor or epithelioid trophoblastic tumor. CONCLUSION: For patients with persistent low-level elevated hCG, frequent follow-up rather than any therapy is recommended. Treatment was considered effective and safe once diagnosis of active malignancy was confirmed.

Generation of a Specific Fluorescence In Situ Hybridization Test for the Detection of Ovarian Carcinoma Cells.

Examinations of ovarian cancer cells require the ability to identify tumor cells. Array-based comparative genome hybridization (aCGH) on 30 ovarian carcinomas (OC) identified three genomic loci (8q24.23; 17p12; 18q22.3) over- or under-represented in OC. A fluorescence in situ hybridization (FISH) probe of these three loci is intended to identify tumor cells by their signal pattern deviating from a diploid pattern. Human DNA from these three loci is isolated from bacterial artificial chromosomes (BAC), amplified and labeled with fluorescent dyes. After a standard FISH procedure, 71 OC suspensions from primary tumors, three OC cell lines, three lymphocyte suspensions, and one mesenchymal cell line LP-3 are analyzed with a fluorescence microscope. On average, 15% of the lymphocytes deviate from the expected diploid signal pattern, giving a cut-off of 36%. If this value is exceeded, tumor cells are detected. The mesenchymal cell line LP-3 shows only 21% as a negative control. The OC cell lines as positive controls exceed this value at 38%, 67%, and 54%. Of the 71 OC primary cultures, four cases fell below this cut-off as false negatives. In the two-sample t-test, the percentages of conspicuous signal patterns differ significantly.

Case report: Squamous cell carcinoma and spindle cell sarcoma (SCS) arising in a mature cystic teratoma of the ovary.

Objective: Malignant transformation of mature ovarian teratoma is a rare phenomenon, mainly occurring in postmenopausal period. Squamous cell carcinoma accounts for 80% of all malignant transformations. Sarcoma transformation is much less common and tends to imply a poorer prognosis and aggressiveness. Case report: We report a case of undifferentiated sarcoma with squamous cell carcinoma in a mature cystic teratoma of the ovary in a 36-year-old woman. The tumor shows epithelial and stromal components. This is a unique report of a benign teratoma of the ovary with malignant transformation, showing epithelial and sarcomatous components. This young woman presented with abdominal distension and a rapidly enlarging ovario-derived pelvic mass with a slightly elevated CA199 tumor marker of 115.9 U/ml. The woman underwent transabdominal excision of the left ovarian cyst on October 20, 2020. During the operation, rapid freezing pathological examination did not indicate malignancy. The postoperative paraffin pathology revealed undifferentiated sarcoma with squamous cell carcinoma (from mature cystic teratoma malignancy), and she finally received comprehensive staging surgery. Postoperative paraffin pathology showed no residual cancer in uterus and other tissues, and all lymph nodes were negative. The patient was finally diagnosed with ovarian malignant tumor IC1 stage (high-grade spindle cell sarcoma complicated with squamous cell carcinoma). Chemotherapy was completed three times after surgery, and no signs of recurrence were found after follow-up. Conclusion: The preoperative diagnosis and intraoperative rapid freezing examination of malignant transformation of mature teratoma of ovary are challenging.

Gastric-type Mucinous Carcinoma with an Abnormal Increase of CA199: A Case Report and Literature Review.

Objective: Gastric-type mucinous carcinoma (GAS), as a rare subtype of mucinous adenocarcinoma, accounts for approximately 1%-3% of cervical adenocarcinoma. It was considered as a new type of cervical mucinous adenocarcinoma by the World Health Organization (WHO) in 2014. GAS represents more aggressive disease than does usual type endocervical adenocarcinoma (UEA). Case report: A case of cervical adenocarcinoma with an abnormal increase of CA199 in a 50-year-old Chinese woman was reported. Our patient presented with abnormal vaginal discharge and combined with elevated Ca199 at the value of 2,729 U/mL. Imaging examinations showed no abnormalities. Diagnostic conical resection suggested cervical adenocarcinoma in situ. Post-operative pathology confirmed mucinous cervical adenocarcinoma (considering gastric type), infiltrating cervical interstitial >2/3, involving the deep myometrium, accompanied by vascular carcinoma infiltration and lymph node metastasis.The patients received an extensive hysterectomy and post-operative adjuvant chemoradiotherapy. The chemotherapy regimen was paclitaxel, combined with platinum. After 20 months of follow-up, the patient showed no signs of recurrence. Conclusion: Preoperative diagnosis of cervical adenocarcinoma is insidious and can be easily misdiagnosed. For patients with high preoperative Ca199, the possibility of GAS should be kept open.

Lamivudine vs placebo or no treatment in preventing the transmission of hepatitis B virus during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infection is a severe health problem, especially in developing countries. Almost 45% of the population lives in highly endemic areas, where the most common form of transmission is mother to child transmission (MTCT). Administration of antiviral therapy has been established. Nevertheless, its efficacy still remains controversial. METHODS: We conducted the current study to fully evaluate the effectiveness of lamivudine in preventing the MTCT of HBV based on randomized controlled trials (RCTs). Four English electronic databases and four Chinese electronic databases were searched from the inception of each database to 26 September 2017. Studies were included if they (1) were human RCT studies, (2) indicated exposure to lamivudine, (3) explicitly indicated control to placebo or no treatment, (4) indicated the participants were pregnant women infected with HBVand (5) compared the outcome of interest as the MTCT. Extracted data were tabulated and analyzed using Review Manager. RESULTS: Eleven RCTs were included and analyzed. Compared with controls (placebo or no treatment), lamivudine significantly reduced the probability of MTCT, as indicated by newborn HBsAg seropositivity (RR=0.44, 95% CI 0.26 to 0.74, I2=41%), HBeAg seropositivity (RR=0.66, 95% CI 0.36 to 1.19, I2=0%) and HBV DNA seropositivity (RR=0.29, 95% CI 0.18 to 0.4`6, I2=0%) within 24 h after birth. Similar results were noted pertaining to infant HBsAg seropositivity and HBV DNA seropositivity within 6-7 and 12 mo. CONCLUSIONS: Lamivudine can significantly reduce the MTCT of HBsAg and HBV DNA of neonates during the third trimester of pregnancy without severe adverse events.

Epithelioid trophoblastic tumor that requires fertility preservation: A case report and review of literature.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is very rare and few cases have been published in the English literature. Hysterectomy is the recommended treatment, due to the high rate of recurrence and mortality. The objective of this article is to present a rare case of ETT with fertility-preserving treatment and review published similar cases. CASE REPORT: We report the case of ETT in a 19-year-old Chinese woman, who had a strong desire of fertility preservation. She presented with vaginal spotting and hysteroscopy showed an isolated solid mass (2.0 × 1.5 × 1.5 cm) at the right corner of the uterine cavity. Serum ß-human chorionic gonadotropin (ß-HCG) persisted at low level elevation about 100 IU/L. We treated her with a lesionectomy and 3 cycles EP-EMA (etoposide, cisplatin/etoposide, methotrexate and actinomycin) chemotherapy regimen. The patient is now in stable condition, without any signs of recurrence during 20 months of follow-up. CONCLUSION: Fertility-preserving surgery would probably be a feasible and safe strategy for the patients whose lesions can be completely removed.

Synchronous occurrence of benign mesothelioma and adenomatoid tumor of uterus: A case report and review of literature.

INTRODUCTION: Synchronous occurrence of benign cystic mesothelioma and adenomatoid tumor of uterus (UAT) are very rare and few cases have been published in the English literature. They are easily misdiagnosed as malignant by clinicians, due to the lack of reports. PATIENT CONCERNS: A case of benign mesothelial combined with uterus adenomatoid tumor (UAT) in a 48-year-old Chinese woman was reported. Our patient presented with abdominal pain and surgery showed a large subserous mass (12.0 × 11.4 × 9.8 cm) combined with a small intramural solid nodule (2.0 × 1.0 × 1.0 cm), and multiple minute neoplastic growth on the ovary. DIAGNOSIS: Due to the patient's symptoms, pathological findings, she was diagnosed with synchronous occurrence of benign mesothelioma and UAT. INTERVENTIONS: We treated her with a total hysterectomy and bilateral adnexectomy. OUTCOMES: The patient is now in stable condition, without any signs of recurrence during 1 year of follow-up. LESSONS: Most mesotheliomas are malignant, synchronous occurrence of benign mesothelioma and UAT are extremely rare. And they are often misdiagnosed as malignancy by clinicians. Our case report can improve the awareness of the disease and avoid excessive treatment.