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.

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.

The genes CNV features in the tumor cells in patients with ovarian serous adenocarcinoma.

e13641 Background: Serous adenocarcinoma is the most common subtype of ovarian cancer. Early diagnosis of this disease can significantly improve the prognosis. Development of more effective methods for early diagnosis and identification of more reliable markers require understanding the molecular mechanisms underlying the malignant behavior of ovarian epithelial cells. The aim of the study was to analyze the copy number variation (CNV) of genes that regulate apoptosis, DNA repair, cell proliferation, metabolism and estrogen reception in tumor and normal ovarian cells. Methods: For the study, we used tissue sections from FFPE blocks of 65 patients with serous ovarian adenocarcinoma diagnosis. Tumor and normal ovarian epithelial cells were isolated using laser microdissection with non-contact capture (Palm MicroBeam, Carl Zeiss). DNA was extracted from cells using the phenol-chloroform method. CNV of 33 genes (BRAF, KRAS, EGFR, PIK3CA, PTEN, TP53, BRCA1, BRCA2, PRKCI, NOTCH1, AKT1, BAX, CASP7, CASP3, CASP8, CASP9, MDM2, BCL2, CYP1A1, CYP1A1, CYP1A2, CYP1A2, CYP1A2, CYP1A1, CYP1A2, CYP1, ESR2, GPER, STS, SULT1A, SULT1E1, OCT4, SOX2, C-MYC, SOX18, SCNN1A) were determined by Real-Time qPCR method (reference B2M, GAPDH). Statistical analysis was performed using the Mann-Whitney test. For cluster analysis (Hierarchical Clustering, Euclidean distance) scripts in R were used. Results: A statistically significant (p < 0.005) increase in the CNV of PTEN, MDM2, SOX2, CYP1B1, ESR1, and SULT1E1 by 2.0, 2.0, 1.8, 2.5, 3.0 and 2.0 times, respectively, was found, as well as a 2.0-fold decrease in the CNV of CASP3 and CASP8 in tumor cells relatively to normal ones. Cluster analysis allowed us to distinguish 2 groups of serous adenocarcinoma samples that differed in gene CNV (p < 0.005): in group 1 (n = 40), the copy number of the SOX2, MDM2, ESR1, CYP1B1 and SULT1E1 genes was increased and the copy number of the TP53 and BRCA2 genes was reduced, in group 2 (n = 25), copy number of PTEN, PIK3CA, BCL2 was increased and copy number of BAX, CASP3 and CASP8 was lower. Conclusions: CNV analysis revealed the most characteristic markers of ovarian serous adenocarcinoma cells. Based on the differential CNV, 2 molecular subtypes of serous adenocarcinoma were distinguished.

Synchronous Cervical Adenocarcinoma and Ovarian Serous Adenocarcinoma—A Case Report and Literature Review

Background/Aim: Synchronous gynecological malignancies are rarely encountered, and most often these cases are represented by synchronous ovarian and endometrial cancer. The aim of this paper is to present the case of a 53-year-old patient who was diagnosed with synchronous cervical and ovarian cancer. Case presentation: The patient had been initially investigated for vaginal bleeding and was submitted to a biopsy confirming the presence of a cervical adenocarcinoma. Once the diagnostic of malignancy was confirmed, the patient was submitted to a computed tomography which revealed the presence of large abdominal tumoral nodules of peritoneal carcinomatosis and was submitted to palliative chemotherapy with poor response. Eighteen months later she developed intestinal obstruction and was submitted to surgery. At that moment, synchronous ovarian and cervical tumors were diagnosed. Total radical hysterectomy with bilateral adnexectomy, pelvic and para-aortic lymph node dissection, omentectomy, and pelvic peritonectomy was performed; in the meantime, the histopathological studies confirmed the presence of two synchronous malignancies. Conclusion: Although synchronous lesions are rarely encountered, this eventuality should not be omitted. In such cases, surgery should be taken in consideration and the intent of radicality should regard both lesions.