Detection of BRCA1/2 Mutation and Analysis of Clinicopathological Characteristics in 141 Cases of Ovarian Cancer

Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) are known biomarkers for hereditary ovarian cancer (OC). However, a comprehensive association study between BRCA1/2 mutation spectrum and clinicopathological characteristics in Chinese ovarian cancer patients has not been performed yet to our best knowledge. To fill in this gap, we collected BRCA1/2 sequencing data and clinical information of 141 OC patients from Fujian Cancer Hospital between April 2018 and March 2020. The clinical information includes the age of onset, FIGO staging, pathological types, serum 125 detection level, lymph node metastasis, distant metastasis, the expression of Ki67, and disease history of the patient and his/her family. We then studied their associations by software SciPy 1.0. As a result, we detected pathogenic and potentially pathogenic BRCA1/2 mutations in 27 out of 141 patients (19.15%). Among the 27 patients with mutations, the major type of mutation was frameshift, which was observed in 12 patients (44.4%). Most of the mutation sites were distributed on exons 10 and 11, accounting for 48.1% (13/27) and 22.2% (6/27), respectively. In terms of histological classification, high-grade serous adenocarcinoma accounted for 79.43% of the 141 samples. The BRCA1/2 mutation group was all high-grade serous adenocarcinoma, accounting for 24.1% (27/112) of this group. The incidence of pathogenic mutation in BRCA1 and BRCA2 was 15.7% (19/112) and 7.27% (8/112), respectively. Univariate analysis showed that there was no significant difference between patients with BRCA1/2 mutation and others in age-of-onset, FIGO stage, pathological types, serum CA125 level, lymph node metastasis, the expression of Ki67, and personal and family disease history. However, there are significant differences between patients with BRCA1/2 mutation and others in distant metastasis rate ( P < 0.002 ). In addition, the BRCA1/2 mutation rate in 141 ovarian cancer patients was similar to those reported in other studies in China. Nearly one-quarter of high-grade serous carcinomas had BRCA1/2 mutations. In conclusion, our study indicated that patients with BRCA1/2 mutations were more likely to undergo distant metastasis, and BRCA1/2 mutation detection should be performed for patients with high-grade serous adenocarcinoma to guide the selection of clinical treatment options.

Low-Grade Ovarian Serous Adenocarcinoma with Lymph Node Metastasis in Neck

Low-grade ovarian serous adenocarcinoma is rarely encountered in the neck region. The diagnosis of this rare malignancy entity in the neck is challenging for both clinicians and pathologists. A 53-year-old female with a chief complaint of a right lower neck mass that had been growing for approximately 2 weeks. The ultrasound-guided fine needle aspiration cytology favored malignancy. The positron emission tomography/computed tomography scan revealed the clustered enlarged lymph nodes with increased radioactivity uptake in the right neck level V, and strong radioactivity uptake was also displayed in the right ovarian regions. Pelvis magnetic resonance imaging displayed right adnexal complex mass supporting the ovarian cancer. An en bloc resection of the right neck lymph node was conducted. Ovarian serous adenocarcinoma with metastasis of lymph nodes in the neck was confirmed through histopathological findings. This study reviews the clinical features of low-grade ovarian serous carcinoma metastasizing to lymph nodes in neck. Although very rare, ovarian cancer with neck metastasis should be considered in the differential diagnosis of a neck mass lesion. The clinical staging would be relatively high due to the quiet entity of the cancer.

Cytology of peritoneal implants of borderline serous tumor of ovaries in ascitic fluid

Objectives: Peritoneal fluid cytology is done routinely in cases with serous carcinoma of ovary. However, morphologic features of borderline serous tumors (BSTs) of ovary in ascitic fluid have been rarely described. The aim of our study was to evaluate the morphologic features of BST with and without ascitic fluid involvement (BST+ and BST-, respectively) and compare with those of serous carcinomas, both in conventional and liquid-based cytology (LBC) smears. Material and Methods: Out of 30 BST cases reported in 3 years, seven cases had BST+. We compared the cytomorphology of seven cases of BST+, seven cases of BST-, and seven cases of serous adenocarcinoma with positive ascitic fluid cytology. Both conventional and LBC smears were studied in all cases and compared. Histopathology of omentum in these cases was also studied. Results: Most cases with BST+ had regular papillary fragment borders with nuclei showing mild-to-moderate pleomorphism, fine nuclear chromatin with small nucleoli as compared with serous carcinomas all of which had irregular borders with moderate-to-severe nuclear pleomorphism, coarse chromatin, and macronucleoli. Conclusion: A combination of cytoarchitectural and nuclear features can help in suspecting BST in ascitic fluid. Ascitic fluid cytology together with tissue histology can increase the rate of the detection of peritoneal implants.

Characteristics of hematopoiesis in primary and recurrent ovarian cancer

Introduction. An important aspect of cancer treatment today is the concept of immuno-targeted therapy, which requires a deep understanding of the characteristics of immune reactions in the body of a cancer patient. Bone marrow is the central organ of immunopoiesis, therefore, along with the study of tumor characteristics, attention is paid to the bone marrow. The study of the cellular composition of the bone marrow in some types of cancer revealed a number of features of hematopoiesis, which requires further deeper analysis.Purpose. To study the parameters of hematopoiesis in patients with primary and recurrent ovarian cancer.Materials and methods. The paper presents data from 68 patients with a verified diagnosis of primary (n = 43) and recurrent (n = 25) ovarian cancer. The study was dominated by serous adenocarcinoma of high grade. Stage I was established in 13.2 % of cases, II – in 5.9 %, III – in 60.3 %, IV – in 20.6 %. The bone marrow was harvested by puncture of the posterior iliac spine (spina iliaca posterior superior). Parameter assessment and myelogram calculation were performed by two physicians, morphologists. The content of myelokaryocytes, indicators of granulocyte, erythroid lineage, the content of lymphocytes, monocytes were analyzed, and myelogram indices were assessed. In all patients microscopy of bone marrow samples excluded metastatic lesions. Statistical data processing was performed using the SPSS Statistics v. 21 package.Results. The analysis of bone marrow samples from patients with ovarian cancer revealed differences with the norm for both primary and recurrent ovarian cancer. Most punctates were normocellular, but average myelokaryocyte count in both groups was below normal. With recurrent ovarian cancer, a reduced content of promyelocytes and metamyelocytes was noted, whereas with primary cancer, all young forms of neutrophils was below normal. An increase in segmented neutrophils without a change in the percentage of cells of the granulocytic lineage was observed in primary ovarian cancer, and in one third of the samples of bone marrow an increased number lymphocytes and monocytes were noted. With recurrent ovarian cancer lymphocytes were increased in 2/3 of samples, monocyte – in 48 %. A change in the proportion of cells of the erythroid lineage was observed in both recurrent and primary cancers: depletion of the pool of basophilic normoblasts and polychromatophils with an unchanged number of erythrokaryocytes, an increase in oxyphilic forms were noted.Conclusion. The revealed changes in hematopoiesis in ovarian cancer reflect the aggressive course of high-grade tumors, which can be considered as a result of the systemic influence of the tumor, and the obtained data can serve as the basis for a detailed immunophenotypic study of bone marrow in ovarian cancer.

Added value of contrast-enhanced ultrasound (CEUS) in the diagnosis of primary retroperitoneal serous adenocarcinoma: a case report

Background Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignant disease. Given the rarity of the disease, the imaging features of PRSA are unclear. Contrast-enhanced ultrasound (CEUS) also plays an important role in the evaluation of the differential diagnosis of retroperitoneal lesions. Case presentation We report the case of a 62-year-old woman of with increased CA125 levels for 1 year who was referred to our hospital. After conducting contrast-enhanced computed tomography and magnetic resonance imaging, the mass was misdiagnosed as a chocolate cyst. After transvaginal ultrasound (TUS) combined with CEUS, cystadenocarcinoma was considered as the initial diagnosis. Pathology results confirmed PRSA as the final diagnosis. Conclusions CEUS features of PRSA are reported for the first time based on this case, potentially aiding in the differential diagnosis of this rare entity before surgery.

Implication of BAG5 Downregulation in Metabolic Reprogramming of Cisplatin-resistant Ovarian Cancer Cells via mTORC2 Signaling Pathway

Background: Ovarian cancer is the most frequent cause of death among gynecologic malignancies due to the absence of an early effective diagnostic approach. Although the majority of patients typically respond well to the first line of chemotherapy based on platinum compounds and taxanes, recurrence and chemoresistance limits its clinical utility. Remarkably, cancer stem cells (CSC) tend to form minimal residual disease after chemotherapy and exhibit recurrent potential. The ability of cancer cells to reprogram their metabolism has recently been related with resistance to chemotherapies.Methods: BAG5 expression was studied in 16 cisplatin-sensitive and 8 cisplatin-resistant ovarian cancer tissues by Western blot. BAG5-induced cell proliferation, migration and invasion were investigated by CCK-8 assay, colony formation assay, wound healing and Transwell assay. To investigate whether BAG5 is implicated in metabolism regulation, mitochondrial function was monitored by real-time measurement of changes in the oxygen consumption rate (OCR) and glycolysis was also determined by measuring the extracellular acidification rate (ECAR). Immunohistochemical staining measured correlations between BAG5 and Bcl6, Rictor in most ovarian serous adenocarcinoma tissues.Results: The current study found BAG5 expression was decreased in cisplatin-resistant ovarian cancer cells and clinical tissues. Our data demonstrated that BAG5 knockdown was implicated in metabolic reprogramming and maintenance of cancer stem cell (CSC)-like features of cisplatin-resistant ovarian cancer cells via regulation of Rictor and subsequent mTORC2 signaling pathway. In addition, the current study demonstrated that Bcl6 upregulation was responsible for repression of BAG5 transactivation via recruitment on the BAG5 promoter in cisplatin-resistant ovarian cancer. The current study also demonstrated reverse correlations between BAG5 and Bcl6, BAG5 and Rictor in ovarian serous adenocarcinoma tissues. Conclusions: Collectively, the current study identified the implication of Bcl6/BAG5/Rictor-mTORC2 signaling pathway in metabolic reprograming and maintenance of CSC-like features including cisplatin-resistance in cisplatin-resistant ovarian cancer cells. Therefore, further studies on the mechanism underlying regulation of metabolic reprogramming and CSC-like characteristics of cisplatin-resistant ovarian cancer cells may contribute to the establishment of novel therapeutic strategy for cisplatin-resistance.