Ovarian Serous Adenocarcinoma Research Articles

Mesenteric Panniculitis Appears as Metastatic Disease on 18F-FDG-PET/CT Scan.

Mesenteric panniculitis is a rare benign inflammatory process involving mesenteric adipose tissue and the pathogenesis is still unknown. It may present 18Fluorine-fluorodeoxyglucose (18F-FDG) uptake and appear like a malign tumor or metastatic disease. We report a case of 47 year-old woman with serous ovarian adenocarcinoma demonstrating intense 18F-FDG uptake and hyperdense nodularity in mesenteric fatty tissue on post-chemotherapy positron emission tomography/computed tomography imaging. The serum tumor marker (CA-125) level was within the normal range. A correlative magnetic resonance imaging highlighted the diagnosis of mesenteric panniculitis that was also confirmed by clinical follow-up.

Spectrum of BRCA1/2 Mutations in Romanian Breast and Ovarian Cancer Patients.

Background: About 10,000 women are diagnosed with breast cancer and about 2000 women are diagnosed with ovarian cancer each year in Romania. There is an insufficient number of genetic studies in the Romanian population to identify patients at high risk of inherited breast and ovarian cancer. Methods: We evaluated 250 women of Romanian ethnicity with BC and 240 women of Romanian ethnicity with ovarian cancer for the presence of damaging germline mutations in breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively) using Next-Generation Sequencing (NGS) technology. Results: Of the 250 breast cancer patients, 47 carried a disease-predisposing BRCA mutation (30 patients (63.83%) with a BRCA1 mutation and 17 patients (36.17%) with a BRCA2 mutation). Of the 240 ovarian cancer patients, 60 carried a BRCA mutation (43 patients (72%) with a BRCA1 mutation and 17 patients (28%) with a BRCA2 mutation). In the BRCA1 gene, we identified 18 variants (4 in both patient groups (ovarian and breast cancer patients), 1 mutation variant in the BC patient group, and 13 mutation variants in the ovarian cancer patient group). In the BRCA2 gene, we identified 17 variants (1 variant in both ovarian and breast cancer patients, 6 distinct variants in BC patients, and 10 distinct variants in ovarian cancer patients). The prevailing mutation variants identified were c.3607C>T (BRCA1) (18 cases) followed by c.5266dupC (BRCA1) (17 cases) and c.9371A>T (BRCA2) (12 cases). The most prevalent mutation, BRCA1 c.3607C>T, which is less common in the Romanian population, was mainly associated with triple-negative BC and ovarian serous adenocarcinoma. Conclusion: The results of our analysis may help to establish specific variants of BRCA mutations in the Romanian population and identify individuals at high risk of hereditary breast and ovarian cancer syndrome by genetic testing.

CLO22-060: > 3 Courses of Neo-Adjuvant Chemotherapy (NACT) May Affect Outcomes of Advanced Ovarian Serous Adenocarcinoma Patients

CLO22-060: > 3 Courses of Neo-Adjuvant Chemotherapy (NACT) May Affect Outcomes of Advanced Ovarian Serous Adenocarcinoma Patients

Multi-scale Pan-cancer Integrative Analyses Identify the STAT3-VSIR Axis as a Key Immunosuppressive Mechanism in Head and Neck Cancer.

VSIR is a novel immune checkpoint protein whose expression on tumor cells across cancers remains largely uncharacterized. Here we purposed to decode the pan-cancer biologic and clinical significance of VSIR overexpression in the tumor compartment. We performed multi-omics integrative analyses of 9,735 tumor samples to identify cancers with non-leukocytic expression of VSIR (VSIR High), followed by association with overall survival and immune cell infiltration levels. Orthogonal assessments of VSIR protein expression and lymphocytic infiltration were performed using quantitative immunofluorescence (QIF). Integrative modeling identified a subset of cancer types as being enriched for VSIR High tumors. VSIR High tumors were associated with significantly poorer overall survival in immunogenic ovarian serous adenocarcinoma (SA) and oral cavity squamous cell carcinoma (SCC). QIF assessments in an independent validation cohort confirmed overexpression of VSIR as being associated with poorer overall survival within immunogenic oral cavity SCC. VSIR overexpression was associated with lower CD4 helper T-cell infiltration in both ovarian SA and oral cavity SCC, but did not impact CD8 T-cell infiltration. VSIR overexpressing tumors in both cancer types exhibited significantly higher STAT3 signaling activity. Pharmacologic inhibition of STAT3 signaling resulted in dose-dependent reduction of VSIR expression in ovarian SA and oral cavity SCC cells. The STAT3-VSIR axis is a potentially significant immunomodulatory mechanism in oral cavity and ovarian cancers, whose activation is associated with poorer survival and an immune microenvironment marked by decreased CD4 helper T-cell activity. The role of VSIR as a tumor-intrinsic modulator of resistance to immunotherapy warrants further exploration.

Analysis of the malignant ovarian tumors incidence in the Sumy region in 2014-2018.

Background. Ovarian cancer is a very important pathology of the female reproductive system and tends to increase in incidence and mortality rates around the world. Despite the fact that ovarian cancer prevalence is lower than that of breast and cervical cancer, its mortality rate is three times higher. Aim. To analyze the incidence of ovarian cancer in the female population of Ukraine and the Sumy region in 2014–2018. Methods. Data from the National Cancer Register of Ukraine were used for this work. A statistical analysis of the incidence rates of ovarian cancer in the population of Ukraine and Sumy region was carried out. Results. The highest incidence of ovarian cancer in the Sumy region was detected in 2018 (12.5 cases per 100,000 women), and the lowest - in 2017 (10.4 cases per 100,000 women). This pathology occurs most often in women 60-79 years old. 91% of the tumors were epithelial-stromal tumors, of which 75% were serous ovarian adenocarcinomas. Ovarian cancer in most cases was diagnosed at the third stage of the disease (47% of cases), which indicates a low level of early diagnosis of this tumor. Conclusion. In the Sumy region, a high incidence rate of ovarian cancer was revealed, which exceeds the national one and has a significant age dependence. Serous ovarian adenocarcinoma is the most common type of ovarian cancer. This pathology is diagnosed mainly at the 3rd stage.

StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42

Metastasis remains the main challenge to overcome for treating ovarian cancers. In this study, we investigate the potential role of the Cdc42 GAP StarD13 in the modulation of cell motility, invasion in ovarian cancer cells. StarD13 depletion does not affect the 2D motility of ovarian cancer cells. More importantly, StarD13 inhibits matrix degradation, invadopodia formation and cell invasion through the inhibition of Cdc42. StarD13 does not localize to mature TKS4-labeled invadopodia that possess matrix degradation ability, while a Cdc42 FRET biosensor, detects Cdc42 activation in these invadopodia. In fact, StarD13 localization and Cdc42 activation appear mutually exclusive in invadopodial structures. Finally, for the first time we uncover a potential role of Cdc42 in the direct recruitment of TKS4 to invadopodia. This study emphasizes the specific role of StarD13 as a narrow spatial regulator of Cdc42, inhibiting invasion, suggesting the suitability of StarD13 for targeted therapy.

A monoclonal antibody against annexin A2 targets stem and progenitor cell fractions in tumors

The involvement of cancer stem cells (CSCs) in driving tumor dormancy and drug resistance is well established. Most therapeutic regimens however are ineffective in targeting these regenerative populations. We report the development and evaluation of a monoclonal antibody, mAb150, which targets the metastasis associated antigen, Annexin A2 (AnxA2) through recognition of a N-terminal epitope. Treatment with mAb150 potentiated re-entry of CSCs into the cell cycle that perturbed tumor dormancy and facilitated targeting of CSCs as was validated by in vitro and in vivo assays. Epigenetic potentiation further improved mAb150 efficacy in achieving total tumor regression by targeting regenerative populations to achieve tumor regression, specifically in high-grade serous ovarian adenocarcinoma.

Long-term experience with percutaneous biopsies of pelvic lesions using CT guidance.

To evaluate the accuracy, efficiency, complication rate, technical features, and relations among followed parameters of CT-guided percutaneous biopsies of the pelvic lesions. 140 biopsies in 136 patients for tumors, sizes 17-160 mm in largest diameter, were carried out in patients with probable tumorous pelvic process within ten years period. The patients were women in 77 cases and men in 59 cases, aged 21 to 87 years. The lesions´ size varied from 17 mm to 160 mm in largest diameter. In 135 biopsies (96.4%) results were true positive or true negative; only 5 procedures (3.6%) were histologically false negative and had to be verified surgically. Metastatic affection was the most common diagnosis (26.4%). Lymphomas were diagnosed in 25%; serous adenocarcinoma of ovary or uterine tube was verified in 15.7% of cases. Totally 7 complications (5%) were confirmed, all were minor hemorrhages. A statistically significant relation between the complication rate and hypervascular character (p = 0.00004), and between needle gauge and histological accuracy (p = 0.00429) was revealed. Core needle biopsy using percutaneous approach and CT guidance had a high overall accuracy in determining the final histological diagnosis including subtyping. Concurrently, the complication incidence was low.

S3084 Metastatic Serous Ovarian Adenocarcinoma Presenting as a GI Bleed

S3084 Metastatic Serous Ovarian Adenocarcinoma Presenting as a GI Bleed

A pancancer overview of FBN1, asprosin and its cognate receptor OR4M1 with detailed expression profiling in ovarian cancer.

Ovarian cancer affects >295,000 women worldwide and is the most lethal of gynaecological malignancies. Often diagnosed at a late stage, current research efforts seek to further the molecular understanding of its aetiopathogenesis and the development of novel biomarkers. The present study investigated the expression levels of the glucogenic hormone asprosin [encoded by fibrillin-1 (FBN1)], and its cognate receptor, olfactory receptor 4M1 (OR4M1), in ovarian cancer. A blend of in silico open access The Cancer Genome Atlas data, as well as in vitro reverse transcription-quantitative PCR (RT-qPCR), immunohistochemistry and immunofluorescence data were used. RT-qPCR revealed expression levels of OR4M1 and FBN1 in clinical samples and in ovarian cancer cell lines (SKOV-3, PEO1, PEO4 and MDAH-2774), as well as the normal human ovarian surface epithelial cell line (HOSEpiC). Immunohistochemical staining of a tissue microarray was used to identify the expression levels of OR4M1 and asprosin in ovarian cancer samples of varying histological subtype and grade, including clear cell carcinoma, serous ovarian cancer and mucinous adenocarcinoma. Immunofluorescence analysis revealed asprosin expression in SKOV-3 and HOSEpiC cells. These results demonstrated the expression of both asprosin and OR4M1 in normal and malignant human ovarian tissues. This research invokes further investigation to advance the understanding of the role of asprosin and OR4M1 within the ovarian tumour microenvironment.

Implication of BAG5 downregulation in metabolic reprogramming of cisplatin-resistant ovarian cancer cells via mTORC2 signaling pathway

Ovarian cancer is the most frequent cause of gynecologic malignancies associated death. Primary or acquired cisplatin resistance is frequently occurred during ovarian cancer therapy. Cancer stem cells (CSC) tend to form minimal residual disease after chemotherapy and are implicated in relapse. The ability of cancer cells to reprogram their metabolism has recently been related with maintenance of CSC and resistance to chemotherapies. The current study found that 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 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. Collectively, the current study identified the implication of Bcl6/BAG5/Rictor-mTORC2 signaling pathway in metabolic reprograming and maintenance of CSC-like features 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.

Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance

Recurrence of therapy-resistant tumors is a principal problem in solid tumor oncology, particularly in ovarian cancer. Despite common complete responses to first line, platinum-based therapies, most women with ovarian cancer recur, and eventually, nearly all with recurrent disease develop platinum resistance. Likewise, both intrinsic and acquired resistance contribute to the dismal prognosis of pancreatic cancer. Our previous work and that of others has established CLPTM1L (cleft lip and palate transmembrane protein 1-like)/CRR9 (cisplatin resistance related protein 9) as a cytoprotective oncofetal protein that is present on the tumor cell surface. We show that CLPTM1L is broadly overexpressed and accumulated on the plasma membrane of ovarian tumor cells, while weakly or not expressed in normal tissues. High expression of CLPTM1L is associated with poor outcome in ovarian serous adenocarcinoma. Robust re-sensitization of resistant ovarian cancer cells to platinum-based therapy was achieved using human monoclonal biologics inhibiting CLPTM1L in both orthotopic isografts and patient-derived cisplatin resistant xenograft models. Furthermore, we demonstrate that in addition to cell-autonomous cytoprotection by CLPTM1L, extracellular CLPTM1L confers resistance to chemotherapeutic killing in an ectodomain-dependent fashion, and that this intercellular resistance mechanism is inhibited by anti-CLPTM1L biologics. Specifically, exosomal CLPTM1L from cisplatin-resistant ovarian carcinoma cell lines conferred resistance to cisplatin in drug-sensitive parental cell lines. CLPTM1L is present in extracellular vesicle fractions of tumor culture supernatants and in patients’ serum with increasing abundance upon chemotherapy treatment. These findings have encouraging implications for the use of anti-CLPTM1L targeted biologics in the treatment of therapy-resistant tumors.

Intraluminal Colon Metastases from Ovarian Serous Adenocarcinoma: An Unusual Site for Metastatic Deposit

Surface epithelial stromal tumors are the most common tumors of the ovary. Hematogenous spread is responsible for the distant metastases. The most common sites of distant metastases are pleura, liver, lung, and bones. Some rare sites of metastases are eyes, skin, breast, CNS, heart, central airways, stomach, colon, and placenta. We report a case of 68-year-old female with serous adenocarcinoma of ovary and synchronous involvement of the colon by poorly differentiated ovarian carcinoma. The diagnosis was confirmed by immunohistochemistry. It is a rare occurrence and it was unusual presentation with ominous prognosis for the patient.

Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations, essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce morbidity.

Gastric Metastasis from Ovarian Carcinoma Revealed by Digestive Hemorrhage: Case Report

The patient is a 71-year-old woman with a serous ovarian cancer hospitalized for asthenia with digestive hemorrhage. At esophagogastroduodenoscopy, a protruding mass was noted at the level of the gastric antrum. She underwent a hemostasis of an endoscopic hemostasis by argon plasma; with effective hemostasis. The final pathology revealed gastric metastases of serous ovarian adenocarcinoma. Weekly gemcitabine chemotherapy was adopted, but the disease progressed rapidly. The patient died 4 months later.

Features of the Copy Number Variation of Certain Genes in Tumor Cells in Patients with Serous Ovarian Adenocarcinoma.

We analyzed the peculiarities of the copy number variation of genes that regulate apoptosis, DNA repair, cell proliferation, metabolism, and estrogen reception in tumor and normal cells of high-grade and low-grade serous adenocarcinoma of the ovaries. Using real-time qPCR method, the relative copy number of 34 genes (BAX, BCL2, TP53, MDM2, CASP9, CASP3, CASP7, CASP8, PRKCI, SOX2, OCT4, PIK3, PTEN, C-MYC, SOX18, AKT1, NOTCH1, BRCA1, BRCA2, EXO1, SCNN1A, KRAS, EGFR, BRAF, CYP1A1, CYP1A2, CYP1B1, CYP19A, ESR1, ESR2, GPER, STS, SULT1A, and SULT1E1) was determined in normal and tumor cells of the ovaries extracted by contactless capture laser microsection from FFPE-blocks of 200 patients. The most typical molecular markers of ovarian serous adenocarcinoma cells were identified: copy number of PIK3CA, BCL2, BAX, CASP3, and CASP8 genes. Based on the differences in the gene copy number variation, two molecular subtypes of serous adenocarcinoma were identified, corresponding to two histological subtypes: high-grade (MDM2, SOX2, ESR1, CYP1B1, SULT1E1, TP53, BRCA2) and low-grade (PIK3CA, PTEN, BCL2, BAX, and CASP3). Each of these subtypes was also characterized by molecular heterogeneity and can be subdivided into several subgroups: 3 subgroups for high-grade and 4 subgroups for low-grade serous adenocarcinoma. These findings extend our understanding of the molecular mechanisms of carcinogenesis in the ovarian tissue, confirm molecular difference between the two histological subtypes of serous adenocarcinoma probably underlying their different clinical course.

Prognostic gene profiles in the tumor microenvironment of ovarian serous adenocarcinoma.

Ovarian serous adenocarcinoma is one of the most common and fatal malignancies among women worldwide. The tumor microenvironment plays a critical role in tumor initiation, proliferation, and metastasis. Immune scores and stromal scores of the tumor microenvironment were determined using the ESTIMATE. Immune cell infiltration was assessed using TIMER and differentially expressed genes (DEGs) were determined using the R/Bioconductor package of edgeR. Survival analysis was carried out using a univariate Cox model and Kaplan-Meier survival, and gene functional information was obtained through Gene Ontology and KEGG pathway analysis. Survival analysis revealed 39 DEGs that significantly influenced the prognosis of ovarian serous adenocarcinoma patients and were correlated with immune cell abundance. Functional enrichment and protein-protein interaction network analyses further indicated that these genes are primarily involved in immune-related responses. Finally, we verified the prognostic value of these genes via GEO. The present results reveal the genes associated with the tumor microenvironment of ovarian adenocarcinoma, potentially providing prognostic information.

Metastatic ovarian cancer to the gallbladder indicative of the diagnosis

Ovarian cancer is a malignant tumor that usually develops from the surface coating of the ovaries. The most common form is epithelial carcinoma. As a result of its location, and its silent nature responsible for a delay in diagnosis that makes the prognosis rather poor. The usual metastatic sites are the peritoneal cavity, liver and lung. Secondary biliary localization is a rare, even exceptional site. We report the observation of a patient who presented with abdominal pain in the right hypochondrium and progressive vomiting. Abdominal ultrasound revealed a 21 mm gallbladder lithiasis with hepatic steatosis. Abdominal CT scan revealed a large heterogeneous mass with engulfed gallstones. The patient underwent cholecystectomy. Histological study showed moderately differentiated adenocarcinoma and acute cholecystitis. Immunohistochemical staining revealed that the tumor cells were positive for antibodies against CK7, WT1, PAX8 and p53 and negative for CK20 and ER. These results suggest that the tumor was a metastasis of serous ovarian adenocarcinoma. Medical imaging done with abdominal CT showed an ovarian mass with peritoneal carcinosis, serum CA125 was elevated at 97U/ml. Carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels were normal. The patient received first-line chemotherapy with carboplatin and paclitaxel. After 6 courses of therapy, she achieved a partial clinical, biological and radiological response, in our medical oncology department of the CHU Hassan II from Fez. The interest of the subject is to report the rarity of this entity as well as the radiological, histopathological, prognostic and therapeutic characteristics.

Anti-GD1b and anti-GM1 positive, acute inflammatory demyelinating polyneuropathy associated with advanced ovarian carcinoma: A case report

Introduction: Paraneoplastic neurological syndromes (PNSs) are mostly associated with non-epithelial ovarian cancers. We report the case of an advanced high-grade serous ovarian adenocarcinoma, diagnosed during the etiological investigation of a subacute motor-sensory axonal neuropathy variant (AMSAN) of Guillain-Barre syndrome (GBS). According to our literature review, only a single case-control study described a positive association between GBS and cancer. Case Report: A 73-year-old woman was admitted to the emergency department for a progressive symmetrical distal tetraparesis, associated with hypoesthesia and abdominal pain. There was no sign of viral or bacterial infection. Over a period of 10 days, she presented a rapid neurological deterioration with nearly complete paralysis of all extremity, facial, and respiratory muscles. The laboratory testing ruled out active infection but the computed tomography (CT) scanner described diffuse peritoneal carcinomatosis, associated with bilateral ovarian tumors. Laparoscopic biopsies confirmed a high-grade serous ovarian cancer. Cerebrospinal fluid analysis confirmed the presence of elevated protein with a normal white blood cell count and anti-ganglioside autoantibodies anti-GD1b and anti-GM1. The patient received systemic chemotherapy together with plasmapheresis and intravenous immunoglobulins, and she experienced a rapid neurological recovery and long-term tumor remission. Conclusion: Neurological paraneoplastic syndromes are rarely associated with epithelial ovarian cancer. Cerebellar ataxia is most frequently associated with this cancer type. Guillain-Barre syndrome can rarely be associated with high-grade serous ovarian cancer. It can delay the tumor diagnosis and treatment. In the case of our patient, early supportive and etiological treatment was of paramount importance for the complete recovery of our patient.

Cancer and Covid-19 in the Department of Internal Medicine and Medical Oncology at the National Teaching Hospital Hubert Koutoukou Maga of Cotonou, about 4 Cases: A Review of the Literature

Coronavirus Disease-19 (COVID-19) manifests itself by a respiratory attack that can go from mild to severe forms. The factors favoring the severe forms are age, arterial hypertension, diabetes mellitus, and cancer. We report 4 cases of COVID-19 on cancer, followed in the Department of Internal Medicine and Medical Oncology of National Teaching Hospital Center Hubert Kougougou Maga (NTHC-HKM). Case 1: A hypertensive 65-year-old female patient with a severe form of COVID-19 on an FIGO (International Federation of Gynecology and Obstetrics) IVB endometrioid adenocarcinoma with pulmonary metastasis: unfavorable evolution under treatment with death. Case 2: A 56-year-old hypertensive patient with severe COVID-19 with pulmonary metastatic recurrence of SBRIII, HER2 positive invasive ductal carcinoma of the left breast: favorable evolution with cure of COVID-19, subsequent death related to active tumor. Case 3: A 37-year-old patient with a moderate form of COVID-19 with hepatocellular carcinoma complicating post alcoholic cirrhosis, CHILD C: favorable evolution with cure of COVID-19, patient lost to follow-up. Case 4: A 56-year-old patient, hypertensive, type II diabetic, presenting a severe form of COVID-19 on a field of ovarian serous adenocarcinoma of high grade FIGO IV A with pleuropulmonary metastasis: favorable evolution with cure of COVID-19, subsequent stroke, patient followed in palliative home hospitalization. The diagnosis of COVID-19 in cancer with pulmonary metastases is difficult. The pulmonary location of tumors seems to be a factor favoring severe forms.