Search

Malignant mesonephric tumor of the uterine cervix is an extremely uncommon subtype of cervical adenocarcinoma with rare, documented cases in the literature. In this report, we present a case of 58 yo, with abdominal pain and ascites that was found to have a synchronous presence of a mesonephric adenocarcinoma of the cervix and advanced serous ovarian carcinoma on the surgical specimen. The histological study identified a tumor showing a mix of tubular and ductal growth patterns. Immunohistochemical analyses were positive for cytokeratin, vimentin, calretinin and CD10. However, the tumor cells were negative for estrogen receptor and progesterone receptor. The patient received neoadjuvant chemotherapy with a combination of carboplatin and gemcitabine followed by optimal debulking surgery and was alive after 18 months of follow up. The management of this rare case remains unclear due to the absence of management guidelines. [ABSTRACT FROM AUTHOR]

Aim: Ovarian serous carcinoma (OSC) and ovarian clear cell carcinoma (OCCC) are two major histological types of epithelial ovarian carcinoma (EOC), each with different biological features and clinical behaviors. Although immunostaining is commonly used for differential diagnosis between OSC and OCCC, correct identification of EOC with mixed-type histology is sometimes a diagnostic challenge. The aim of the present study was to explore candidate genes as potential diagnostic biomarkers that distinguish OSC from OCCC. Methods: A total of 57 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery. Total RNAs were extracted from fresh-frozen tissues of EOC patients, and were used for comprehensive gene expression analysis using DNA microarray technology. Results: Ten candidate genes, FXYD2, TMEM101, GABARAPL1, ARG2, GLRX, RBPMS, GDF15, PPP1R3B, TOB1, and GSTM3 were up-regulated in OCCC compared to OSC. All EOC patients were divided into two groups according to hierarchical clustering using a 10-gene signature. Conclusion: Our data suggest that the 10 candidate genes would be an excellent marker for distinguishing OSC from OCCC. Furthermore, the molecular signatures of the 10 genes may enlighten us on the differences in carcinogenesis, and provide a theoretical basis for OCCC's resistance to chemotherapy in the future. [ABSTRACT FROM AUTHOR]

Background: The most common reason for cancer-related mortality in women is ovarian cancer. Among all histological types, the serous carcinoma is the commonest. Immunotherapy has developed to be used in treating different cancers; among which Immune Checkpoint Inhibitors (ICIs) demonstrated great role in such cases. One of the significant challenges in cancer treatment is the selection of studied cases who will benefit from ICIs. It is established that ICI sensitivity in malignancies can be predicted using Programmed Cell Death Ligand 1 (PD-L1) expression. Prior research has confirmed a correlation among PD-L1 expression in ovarian tumours and Tumour Infiltrating Lymphocytes (TILs). However, regrettably, the Food and Drug Administration (FDA) has not yet approved use of anti-programmed cell death ligand 1 (anti- PD-L1) in the treatment of ovarian cancer. Aim and Scope: This study assesses an immunohistochemical expression of PD-L1 in ovarian serous carcinoma to testify its usage as a prognostic and predictive marker. We also investigate its association with tumor grade, TILs, clinico-pathological prognostic factors, and studied case's survival. Materials and Method: This work is retrospective research performed upon 100 cases of surgically resected ovarian serous carcinomas. Immunohistochemistry (IHC) for PD-L1 was applied to such biopsies then assessed and scored. TILs were also assessed using Haematoxylin and Eosin-stained slides. Finally, the outcomes were tabulated for statistical analysis. Results: In this research, elevated PD-L1 expression had been significantly related to aggressive features of tumor including older age group, larger tumor size, higher tumor grade, advanced International Federation of Obstetrics and Gynecology (FIGO) stage and shorter patients' mean survival time. On the other hand, tumors with positive TILs were significantly associated with younger age group, smaller tumor size, lower tumor grade, early FIGO stage and longer mean survival time. Consistently, PD-L1 overexpression show statistically significant association with tumors showing negative TILs (p ≤ 0.001). Conclusion: We observed PD-L1 overexpression in aggressive features of ovarian serous carcinomas suggesting its poor prognostic and predictive role in such cases that require further studies [ABSTRACT FROM AUTHOR]

We present the case of a 75-year-old female with simultaneous EGFR-mutated stage IV lung cancer and advanced BRCA2-mutated ovarian cancer, treated with a unique regimen. In this case report, the patient was treated with alternating months of osimertinib and olaparib to control her lung and ovarian cancers, respectively. When both diseases showed progression, the patient underwent a trial of concurrent therapy with both drugs, yet this was discontinued due to patient-reported adverse side effects. Combination targeted drug therapy may be required to treat complex diagnoses such as dual malignancies. However, combination drug therapy consisting of osimertinib and olaparib has not previously been explored. This case report represents the first to demonstrate osimertinib and olaparib combination therapy as a unique treatment regimen for concurrent lung and ovarian cancers. These two drugs can either be given in an alternating way or given together, short-term, with a higher but tolerable toxicity profile.

We present the case of a 75-year-old female with simultaneous EGFR-mutated stage IV lung cancer and advanced BRCA2-mutated ovarian cancer, treated with a unique regimen. In this case report, the patient was treated with alternating months of osimertinib and olaparib to control her lung and ovarian cancers, respectively. When both diseases showed progression, the patient underwent a trial of concurrent therapy with both drugs, yet this was discontinued due to patient-reported adverse side effects. Combination targeted drug therapy may be required to treat complex diagnoses such as dual malignancies. However, combination drug therapy consisting of osimertinib and olaparib has not previously been explored. This case report represents the first to demonstrate osimertinib and olaparib combination therapy as a unique treatment regimen for concurrent lung and ovarian cancers. These two drugs can either be given in an alternating way or given together, short-term, with a higher but tolerable toxicity profile. [ABSTRACT FROM AUTHOR]

Abstract Background B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target. Methods A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. Results B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs. Conclusions The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.

Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients. Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Thereafter, immunohistochemical (IHC) staining was used to study the expression patterns of the talin-1 protein using 46 paraffin-embedded OSC tissue specimens, 25 benign tumors, and 20 normal tissues, which were assembled in tissue microarrays (TMAs). We also assessed the potential association between the expression of the talin-1 protein, various clinicopathological parameters, and survival outcomes. Results: Our IHC examination for talin-1 was significantly overexpressed in OSC tissues compared to benign tumors and normal tissues. The Kaplan-Meier survival analysis has also indicated statistically significant differences in terms of diseasespecific survival (DSS) and progression-free survival (PFS) between the patients with high and low expression levels of talin-1, respectively. Conclusion: The talin-1 protein was overexpressed in OSC tissues, and a high expression level of talin-1 was found to be significantly associated with tumor aggressiveness and poorer DSS or PFS. Therefore, talin-1 may serve as a molecular marker of cancer progression and a novel prognostic biomarker in these patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of miR-409-3p on epithelial mesenchymal transition (EMT) of ovarian serous carcinoma HO-8910 cells by targeting ZEB1 and its underlying mechanism. Methods Control mimics and miR-409-3p mimics were transfected into HO-8910 cells by liposomes respectively, and qRT-PCR was adopted to detect the transfection efficiency. The expression of ZEB1, E-cadherin, N-cadherin, and Vimentin proteins in each cell group were examined by Western blotting, and the targeted regulation of ZEB1 by miR-409-3p was determined by dual luciferase reporter assay. Transwell invasion and migration assay was performed to observe the changes of invasion and migration abilities of the cells in each group. Results As compared with the control group, the expression of miR-409-3p was increased significantly in the miR-409-3p overexpression group (P < 0.05), along with the elevation of E-cadherin expression (P < 0.05), while the levels of ZEB1, N-cadherin and Vimentin were decreased remarkably (P < 0.05), suggesting that the EMT process of HO-8910 cells was blocked. Furthermore, the results of dual luciferase reporter assay showed that ZEB1 was the direct target of miR-409-3p; overexpression of ZEB1 reversed the miR-409-3p mimics mediated repression of cell invasion, migration as well as EMT process (P < 0.05). Conclusion Overexpression of miR-409-3p negatively regulates the EMT process by inhibiting ZEB1 expression, and thus suppresses the invasion and metastasis of ovarian serous carcinoma HO-8910 cells.

Background: B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target. Methods: A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. Results: B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs. Conclusions: The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs. [ABSTRACT FROM AUTHOR]

Xinxin Ren,1 Xiang Wang,2 Bi Peng,3 Qiuju Liang,2 Yuan Cai,3 Kewa Gao,3 Yongbin Hu,3 Zhijie Xu,3,4 Yuanliang Yan2 1Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Yuanliang YanDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaEmail yanyuanliang@csu.edu.cnPurpose: To explore the molecular profiles of transcriptional enhanced associate domain (TEAD) family in ovarian serous carcinoma (OSC).Methods: In this study, we use bioinformatics methods including GEPIA, GE-mini, Oncomine 3.0, Kaplan–Meier plotter, cBioPortal, WebGestalt, TIMER2.0 and DiseaseMeth2.0, and in vitro experimental RT-PCR to assess the expression profiles and prognostic significance of TEAD family in OSC.Results: According to the bioinformatics analysis, TEAD family was abnormally expressed in OSC. In terms of prognosis, Kaplan–Meier plotter indicated that OSC patients with high level of TEAD4 showed poor overall survival (OS), progression-free survival (PFS) and post progression survival (PPS). TEAD family also had significantly diagnostic values for OSC patients. Tumor Immune Estimation Resource (TIMER) algorithm indicated that TEAD family was significantly associated with different types of infiltrating immune cells, including B cells, macrophages, dendritic cells, neutrophils, CD8+ T cells and CD4+ T cells. Gene set enrichment analysis of TEAD family-associated coexpression genes was further explored. In in vitro experiments, the RT-PCR results showed the upregulated TEAD2/4 in OSC tissues and cells (A2780 and TOV112D). Moreover, decreased expression of TEAD2 could induce the ferroptosis through increasing the ROS accumulation.Conclusion: Thus, TEAD family correlated with the diagnosis, prognosis and immune infiltration in OSC. These results could provide comprehensive understanding of TEAD family in the diagnosis and prognosis of OSC patients.Keywords: TEAD family, Hippo pathway, ovarian serous carcinoma, expression profiles, prognosis, immune infiltration

Abstract Background Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma. To our knowledge, this is the second case (and the first adult case) confirming the in situ-mimicking growth pattern of a metastatic tumor using immunohistochemistry. Case presentation A 69-year-old Japanese woman was found to have a breast mass with microcalcifications. She had a known history of ovarian mixed serous and endocervical-type mucinous (seromucinous) carcinoma. Needle biopsy specimen of the breast tumor revealed adenocarcinoma displaying an in situ-looking tubular architecture in addition to invasive micropapillary and papillary architectures with psammoma bodies. From these morphological features, metastatic serous carcinoma and invasive micropapillary carcinoma of breast origin were both suspected. In immunohistochemistry, the cancer cells were immunoreactive for WT1, PAX8, and CA125, and negative for GATA3, mammaglobin, and gross cystic disease fluid protein-15. Therefore, the breast tumor was diagnosed to be metastatic ovarian serous carcinoma. The in situ-looking architecture showed the same immunophenotype, but was surrounded by myoepithelium confirmed by immunohistochemistry (e.g. p63, cytokeratin 14, CD10). Thus, the histogenesis of the in situ-like tubular foci was could be explained by the spread of metastatic ovarian cancer cells into existing mammary ducts. Conclusion Metastatic tumors may spread into mammary duct units and mimic an in situ carcinoma component of primary breast cancer. This in situ-mimicking growth pattern can be a potential pitfall in establishing a correct diagnosis of metastasis to the breast. A panel of breast-related and extramammary organ/tumor-specific immunohistochemical markers may be helpful in distinguishing metastatic tumors from primary tumors.

Genetically engineered mice have been the gold standard in modeling tumor development. Recent studies have demonstrated that genetically engineered organoids can develop subcutaneous tumors in immunocompromised mice, at least for organs that prefer predominant driver mutations for tumorigenesis. To further substantiate this concept, the fallopian tube (FT), a major cell of origin of ovarian high‐grade serous carcinoma (HGSC), which almost invariably carries TP53 mutations, was investigated for p53 inactivation‐driven tumorigenesis. Murine FT organoids subjected to lentiviral Cre‐mediated Trp53 deletion did not develop tumors. However, subsequent suppression of Pten and simultaneous induction of mutant Pik3ca led to the development of carcinoma in situ and HGSC‐like tumors, respectively, whereas concurrent deletion of Apc resulted in the development of benign cysts, mirroring frequent activation of the PI3K/AKT axis and the marginal impact of Wnt pathway activation in HGSC. Consistent with the frequent activation of the RAS pathway in HGSC, mutant Kras cooperated with Trp53 deletion for the development of tumors, which unexpectedly contained sarcoma cells in addition to carcinoma cells, despite the epithelial origin of the inoculated organoids. This finding is in sharp contrast with the exclusive adenocarcinoma development from gastrointestinal organoids with the same genotype reported in previous studies, suggesting a tissue‐specific epithelial–mesenchymal transition program. In tumor‐derived organoids, the Cre‐mediated recombination rate reached 100% for Trp53 but not for the other genes, highlighting the advantage of p53 inactivation in FT tumorigenesis. The Trp53 wildtype FT organoids expressing the mutant Kras developed sarcoma and carcinoma upon Cdkn2a suppression and Tgfbr2 deletion, respectively, revealing novel pro‐tumorigenic genetic cooperation and critical roles of TGF‐β signaling for epithelial–mesenchymal transition in FT‐derived tumorigenesis. Collectively, the organoid‐based approach represents a shortcut to tumorigenesis and provides novel insights into the relationships among genotype, cell type, and tumor phenotype underlying tumorigenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract Objective This study is to investigate the relationship between marital status and prognosis of patients with ovarian serous carcinoma. Results We performed data analysis from 19,276 patients identified from the SEER database of the National Cancer Center of the United States. 57.8% of the patients were married, 13.0% unmarried, and 29.2% separated/ divorced/widowed (SDW). The median overall survival time ofthe unmarried group and the married group are 48 months and 52 months respectively. Univariate Cox regression analysis showed that the patients with serous ovarian cancer in the unmarried group resulted in a hazard ratio (HR) of 1.14 (95% CI: 1.08–1.19%; P

Background: Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma. To our knowledge, this is the second case (and the first adult case) confirming the in situ-mimicking growth pattern of a metastatic tumor using immunohistochemistry.Case Presentation: A 69-year-old Japanese woman was found to have a breast mass with microcalcifications. She had a known history of ovarian mixed serous and endocervical-type mucinous (seromucinous) carcinoma. Needle biopsy specimen of the breast tumor revealed adenocarcinoma displaying an in situ-looking tubular architecture in addition to invasive micropapillary and papillary architectures with psammoma bodies. From these morphological features, metastatic serous carcinoma and invasive micropapillary carcinoma of breast origin were both suspected. In immunohistochemistry, the cancer cells were immunoreactive for WT1, PAX8, and CA125, and negative for GATA3, mammaglobin, and gross cystic disease fluid protein-15. Therefore, the breast tumor was diagnosed to be metastatic ovarian serous carcinoma. The in situ-looking architecture showed the same immunophenotype, but was surrounded by myoepithelium confirmed by immunohistochemistry (e.g. p63, cytokeratin 14, CD10). Thus, the histogenesis of the in situ-like tubular foci was could be explained by the spread of metastatic ovarian cancer cells into existing mammary ducts.Conclusion: Metastatic tumors may spread into mammary duct units and mimic an in situ carcinoma component of primary breast cancer. This in situ-mimicking growth pattern can be a potential pitfall in establishing a correct diagnosis of metastasis to the breast. A panel of breast-related and extramammary organ/tumor-specific immunohistochemical markers may be helpful in distinguishing metastatic tumors from primary tumors. [ABSTRACT FROM AUTHOR]

Patients with ovarian serous carcinoma are generally diagnosed at an advanced disease stage. The standard treatment for these patients is maximal debulking surgery followed by platinum-taxane combination chemotherapy. Despite initially responding well, more than half of patients become refractory to first-line chemotherapy. Upregulation of protein arginine methyltransferase 1 (PRMT1) expression has been demonstrated to methylate apoptosis signal-regulated kinase 1 and inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and sensitivity to platinum-based chemotherapy in 51 patients with ovarian serous carcinoma (International Federation of Gynecology and Obstetrics stages III and IV), and the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of ovarian cancer cells to cisplatin and carboplatin in vitro. Immunohistochemistry of tumor specimens was used to compare the expression levels of PRMT1, a Cell Counting Kit-8 assay and small interfering RNA transfection were performed for chemosensitivity assays, and reverse transcription-quantitative PCR was used to examine PRMT1 mRNA expression. Patients were divided into platinum-sensitive (n=26) and platinum-resistant (n=25) groups. PRMT1 expression was significantly lower in the platinum-sensitive group than in the platinum-resistant group (P=0.019). When patients were categorized according to PRMT1 expression, those in the low PRMT1 expression group were more sensitive to platinum-based chemotherapy than those in the high PRMT1 expression group (P=0.01). Additionally, in vitro experiments revealed that suppression of PRMT1 expression by siRNA significantly increased the sensitivity of human ovarian serous carcinoma cells to cisplatin and carboplatin (P<0.05). In conclusion, PRMT1 expression could predict sensitivity to platinum-based chemotherapy in patients with ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Purpose of investigation: To compare low-grade serous ovarian carcinomas (LGSC) and high-grade serous ovarian carcinomas (HGSC). Materials and Methods: Between 1985 and 2013, patients with LGSC and HGSC were identified through pathological review using the 2014 World Health Organization classification. The clinical outcome of patients with LGSC and HGSC was retrospectively compared. Results: A total of 174 cases, 5 (2.9%) cases of LGSC and 169 (97.1%) cases of HGSC (97.1%) were identifies for our study. The proportion of patients who underwent optimal surgery was higher for LGSC than HGSC (p = 0.03). We found no other statistically significant differences in the characteristics of the two groups. Survival analysis revealed that the histological subtype was not an independent prognostic factor of Progression-free survival (p = 0.28) or overall survival (p = 0.43). Conclusions: LGSCs may be a rare histological subtype in Japan and may not be associated with a different prognosis than HGSC. Larger scales studies are needed to examine the clinical significance of LGSC. [ABSTRACT FROM AUTHOR]

Background: Ovarian carcinoma represents 30% of all cancers of the female genital tract, of which high-grade serous carcinomas (HGSCs) are predominant, accounting for 70%. Aims and Objectives: To study the clinicopathological findings and to analyze the postchemotherapy changes in tumors treated with neoadjuvant chemotherapy (NACT). Materials and Methods: All cases diagnosed as ovarian serous carcinoma between 2015 and 2017 at our institute were retrospectively reviewed. Clinical and gross findings were collected, microscopic findings were reviewed, and tumor grade was reassessed as per the World Health Organization 2014 criteria. Chemotherapy response score (CRS) was assessed in cases which received prior chemotherapy. Results: Among malignant ovarian tumors, serous carcinoma was the most common, accounting to 38 cases (44.7%). Of these, six were low-grade serous carcinoma and 32 were HGSC. Among HGSC, six (18.75%) cases showed serous tubal intraepithelial carcinoma. Among 18 (47.4%) cases with prior NACT, CRS-1 was seen in six cases, CRS-2 in seven cases, and CRS-3 in five cases. Cancer antigen (CA)-125 levels were markedly raised in all cases. In six cases postchemotherapy, CA-125 levels were below normal with a CRS-2-3. Omental deposits were seen in 15 (39.47%) cases and showed lesser response to prior NACT compared to tumor in the ovary. Conclusion: HGSC is the most common ovarian serous carcinoma. There is correlation between the biochemical and morphological response to chemotherapy in our study. Pathologists should be well aware of postchemotherapy morphological changes in ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Aim: Ovarian serous carcinoma (OSC) and ovarian clear cell carcinoma (OCCC) are two major histological types of epithelial ovarian carcinoma (EOC), each with different biological features and clinical behaviors. Although immunostaining is commonly used for differential diagnosis between OSC and OCCC, correct identification of EOC with mixed-type histology is sometimes a diagnostic challenge. The aim of the present study was to explore candidate genes as potential diagnostic biomarkers that distinguish OSC from OCCC., Methods: A total of 57 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery. Total RNAs were extracted from fresh-frozen tissues of EOC patients, and were used for comprehensive gene expression analysis using DNA microarray technology., Results: Ten candidate genes, FXYD2, TMEM101, GABARAPL1, ARG2, GLRX, RBPMS, GDF15, PPP1R3B, TOB1, and GSTM3 were up-regulated in OCCC compared to OSC. All EOC patients were divided into two groups according to hierarchical clustering using a 10-gene signature., Conclusion: Our data suggest that the 10 candidate genes would be an excellent marker for distinguishing OSC from OCCC. Furthermore, the molecular signatures of the 10 genes may enlighten us on the differences in carcinogenesis, and provide a theoretical basis for OCCC's resistance to chemotherapy in the future.

Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: This study is to investigate the relationship between marital status and prognosis of patients with ovarian serous carcinoma. Results: We performed data analysis from 19,276 patients identified from the SEER database of the National Cancer Center of the United States. 57.8% of the patients were married, 13.0% unmarried, and 29.2% separated/ divorced/widowed (SDW). The median overall survival time ofthe unmarried group and the married group are 48 months and 52 months respectively. Univariate Cox regression analysis showed that the patients with serous ovarian cancer in the unmarried group resulted in a hazard ratio (HR) of 1.14 (95% CI: 1.08–1.19%; P < 0.001), comparing to SDW group with a HR of 1.02 (95% CI: 0.98–1.19%; P = 0.26). However, the SDW group was not statistically significantly different from the married group. (median 32 vs 52 months). Multivariate Cox regression analysis presented the unmarried group leading to a HR of 1.05 (95% CI: 1.00–1.11%; P = 0.05), and the SDW group was not significant with a HR of 0.99 (95% CI: 0.95–1.03%; P = 0.57). Conclusion: Unmarried patients with ovarian serous carcinoma have higherHRof overall survival. After controlling age, race, grade, radiation and year of diagnosis, unmarried patients were found to have a significantly higher risk of OS. Consequently, these patients are suggested to obtain more focused healthcare for the management of ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Ojective: To investigate the values of combined detection of serum carbohydrate antigen markers in the diagnosis of ovarian serous carcinoma in women before and after menopause. Methods: Used a retrospective study, from August 2016 to February 2018 60 patients with ovarian serous carcinoma before and after menopause (canceration group) and 60 healthy subjects before and after menopause (health control group) were selected, the serum levels of CEA, HE4 and CA125 were detected, and their correlation with clinicopathological features and follow-up prognosis was analyzed. Results: The levels of serum CEA, HE4, CA125 and positive expression rate in the canceration group were significantly higher than those in the healthy control group (P<0.05). Among the 60 patients in the carcinogenesis group, with the increase of pathological stage, reduction of differentiation, lymph node metastasis and mortality, the positive expression rate of serum CEA, HE4 and CA125 increased significantly, the difference was statistically significant (P<0.05). In the 120 cases, there were 54 cases of ovarian serous carcinoma were combined, the sensitivity and specificity of combined diagnosis were 90.0% and 100.0%, respectively. Conclusion: The levels of serum carbohydrate antigen markers CEA, HE4 and CA12 in premenopausal and postmenopausal women with ovarian serous carcinoma were all increased, which may serve as a reference index for the diagnosis and prognosis prediction of ovarian serous carcinoma in premenopausal and postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Recent studies have hypothesized that distal end of fallopian tube is a possible origin of ovarian serous carcinoma. This study investigated histopathological changes in fallopian tube epithelium (FTE) of the patients with ovarian serous tumors compared with control group. Materials and Methods: In a prospective cross-sectional study, fallopian tubes (right and left) of 34 cases with ovarian serous tumors were collected from patients who underwent surgery in two major gynecological centers affiliated to Shiraz University of Medical Sciences, Shiraz, Iran (2012–2015). They are composed of 21 (61.8%) high-grade serous carcinomas (HGSCs), 5 (14.7%) borderline ones, and 8 (23.5%) benign serous tumors. As control group, fallopian tubes of 72 hystrectomy cases without ovarian tumor were added to the study. Both tubes of all of the cases were submitted entirely, according to the protocol of sectioning and extensively examining the fimbriated end. The results were statistically analyzed using SPSS-PC windows and Chi-square tests. Results: Significant differences were found between the cases and control group in tubal epithelial cell stratification (especially >3 cell layers thickness), atypia, mitosis, glandular complexity, tufting, and detached epithelial cells (P < 0.05). These findings particularly atypia and mitosis were more frequently seen in the ampulla and fimbriated end of high-grade ovarian serous carcinomas. Conclusion: Our results showed that premalignant epithelial changes of the ampulla and the distal end of FTE were seen in some of the patients with ovarian HGSCs. Therefore, FTE could be one of the sources of ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Ovarian serous carcinomas have a very large spectrum of growth patterns that contrast with the most primitive ovarian carcinomas, in which the morphology varies very much less. Serous carcinomas growth patterns include papillary and glandular aspects, but also cribriform, solid, microcystic and trabecular, some being common to the both high- and low-grade types of ovarian serous carcinomas, others being distinct. The study included 45 cases of ovarian serous carcinomas out of which five cases with low grade and 40 cases with high grade. High grade serous carcinomas were associated with mixed growth patterns, with large complex papillae, glands with irregular shape lined by stratified epithelia, often with areas of extended necrosis. In the case of low grade ovarian carcinomas we observed the association with more uniform growth patterns, micropapillary or glandular, the presence of optically empty slit-like spaces, psammoma bodies, the absence of necrosis and the association with a borderline or benign component. The recognition of the common histopathological aspects, allows a more accurate diagnosis of the ovarian serous carcinoma types and subtypes, which has a great importance in the actual era of personalized therapy. [ABSTRACT FROM AUTHOR]

The standard treatment for ovarian serous carcinoma is maximum debulking surgery and platinum‑based chemotherapy. Despite the high response rate for chemotherapy, the majority of patients will be resistant to first‑line agents and the prognosis for these patients is particularly poor. Currently there are no reliable methods to determine or predict platinum resistance. Uncoupling protein 2 (UCP2) is widely expressed in cancer cells and regulates the production of mitochondrial reactive oxygen species (ROS). A reduction in ROS is associated with carcinogenesis and chemoresistance. Downregulation of UCP2 significantly causes increased cell death following chemotherapy. The present study investigated the association between UCP2 expression and platinum sensitivity. The study included 54 patients with ovarian serous carcinoma (FIGO stages III and IV) who were treated at Osaka City University Hospital between January 2005 and December 2012. Patients were divided into a platinum‑sensitive group (n=27) and platinum‑resistant group (n=27) based on the platinum‑free interval, which was calculated from the time of last platinum administration to the time of recurrence. UCP2 expression in human ovarian serous carcinoma cells was inhibited by genipin, and changes in carboplatin sensitivity were examined. The UCP2 weighted score was lower in the platinum‑sensitive group than in the platinum resistant‑group (P=0.005). In addition, patients in the low UCP2 expression group were more sensitive to platinum‑based chemotherapy than those in the high UCP2 expression group (P=0.001). Sensitivity to carboplatin was significantly increased when UCP2 was inhibited in human ovarian serous carcinoma cells in vitro. UCP2 expression may be a predictive marker of the efficacy of platinum‑based chemotherapy for patients with ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Eph receptor‑A1 (EphA1) was the first member of the erythropoietin producing hepatocellular carcinoma (Eph) family of receptor tyrosine kinases. Although the roles of EphA1 in the tumorigenesis of various human cancers have been investigated, few studies have focused on ovarian carcinoma. The present study aimed to explore the profile of EphA1 expression in ovarian carcinomas, to analyzed the association between EphA1 expression and clinicopathologic parameters, and to investigate the roles of overexpressed EphA1 in ovarian cancer cells. EphA1 protein was detected in ovarian cancer cell lines and in a set of formalin‑fixed tissues, including normal fallopian tube, ovarian benign serous cystadenoma, borderline serous tumors and serous carcinoma. Ovarian cancer cell lines HO8910 and A2780 were transiently transfected with EphA1‑pCMV6‑GFP plasmid, and the proliferation and apoptosis of cells were measured. The association between EphA1 expression and clinicopathological parameters was statistically analyzed. EphA1 expression was negative in HO8910 and weakly positive in A2780 cells. The proliferation rate was significantly reduced in ovarian cancer cells after transfection with EphA1 plasmid compared with cells transfected with mock plasmid or untreated cells, but no obvious alteration in apoptosis was detected among these groups. EphA1 expression was positively detected in all normal fallopian tubes (10/10, 100%) and ovarian benign serous cystadenomas (12/12, 100%) as well as in some borderline serous tumors (9/15, 60%) and ovarian serous carcinomas (33/76, 43.42%). EphA1 expression was associated with grade of ovarian serous carcinomas, with loss of EphA1 more often observed in high‑grade tumors (P=0.016) and high Ki67 index tumors (P=0.007). These data suggest that EphA1 might be a useful marker for distinguishing low grade from high‑grade ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

The standard treatment for ovarian serous carcinoma comprises maximum debulking surgery and platinum‑based chemotherapy. Despite the high response rate to chemotherapy, the majority of patients will be resistant to first‑line agents and the prognosis for these patients is particularly poor. At present there are no reliable methods to determine or predict platinum resistance. T‑box 2 (TBX2) is widely expressed in cancer cells and is involved in embryonic development and cell cycle regulation. TBX2 enables cells to bypass senescence through its ability to repress the cell cycle regulators p21 and p14ARF; silencing TBX2 induces senescence. Ectopic expression of TBX2 is associated with conferred resistance to the DNA‑damaging chemotherapeutic drugs cisplatin and doxorubicin. In the present study the association between TBX2 expression and platinum sensitivity was investigated. A total of 54 patients with ovarian serous carcinoma (FIGO stages III and IV) were treated at Osaka City University Hospital (Osaka, Japan) from January 2005 to December 2012. Patients were divided into platinum‑sensitive (n=27) and resistant (n=27) groups, according to the platinum‑free interval calculated from the last platinum administration to the time of recurrence. TBX2 expression in human ovarian serous carcinoma cells was inhibited by a TBX2‑specific siRNA and changes in cisplatin and carboplatin sensitivity were determined. The TBX2‑weighted score was significantly lower in the platinum‑sensitive group than the platinum‑resistant group (P=0.005) and the low TBX2 expression group was significantly more sensitive to platinum‑based chemotherapy (P=0.004). Sensitivity to cisplatin and carboplatin significantly increased when TBX2 expression was inhibited in human ovarian serous carcinoma cells in vitro (P<0.05). TBX2 expression may serve as a predictive marker of the efficacy of platinum‑based chemotherapy for patients with ovarian serous carcinoma. [ABSTRACT FROM AUTHOR]

Wnt is a highly conserved signaling pathway responsible for tissue regeneration, maintenance and differentiation of stem cells in adults. Its aberrant activation through reduced expression of Wnt signaling pathway inhibitors, such as proteins from the SFRP family, is commonly seen in many tumors. In the present study we explored SFRP1 protein expression using immunohistochemistry in 11 low-grade serous ovarian carcinomas (LGSC), 42 high-grade serous ovarian carcinomas (HGSC), and 5 normal ovarian tissues (controls). SFRP1 gene methylation was analyzed by methylation-specific PCR in 8 LGSCs, 13 HGSCs and control samples. SFRP1 gene was unmethylated and SFRP1 protein expression was strong in normal ovaries (n = 5). Although SFRP1 gene was unmethylated in almost all of the LGSC cases (7/8, 88%), SFRP1 protein expression was significantly lower than in normal ovaries (p < 0.05). Seven out of 13 HGSCs (54%) showed SFRP1 gene hypermethylation and protein expression level was also significantly lower than in normal ovaries (p < 0.001). Our preliminary data show loss of SFRP1 protein expression caused by the SFRP1 promoter hypermethylation in a subset of HGSCs. SFRP1 protein expression was also lost in LGSCs but different regulatory mechanisms may be involved. Further studies should elucidate the clinical and therapeutic relevance of the observed molecular alterations. [ABSTRACT FROM AUTHOR]

Background Epithelial ovarian cancer (EOC) is an aggressive and heterogeneous disease. < 10% of EOC demonstrate HER2/neu 3 + receptor over-expression. However, moderate to low (i.e., 2 + and 1 +) HER2/neu expression is reported in up to 50% of EOC. The objective of this study was to compare the anti-tumor activity of SYD985, a novel HER2-targeting antibody-drug conjugate (ADC), to trastuzumab emtansine (T-DM1) in EOC models with differential HER2/neu expression. Methods The cytotoxicity of SYD985 and T-DM1 was evaluated using ten primary EOC cell lines with 0/1 +, 2 +, and 3 + HER2/neu expression in antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability and bystander killing experiments. Finally, the in vivo activity of SYD985 and T-DM1 was also studied in ovarian cancer xenografts. Results SYD985 and T-DM1 induced similar ADCC in the presence of peripheral blood lymphocytes (PBL) against EOC cell lines with differential HER2/neu expression. In contrast, SYD985 was 3 to 42 fold more cytotoxic in the absence of PBL when compared to T-DM1 ( p < 0.0001). Unlike T-DM1, SYD985 induced efficient bystander killing of HER2/neu 0/1 + tumor cells when admixed with HER2/neu 3 + EOC cells. In vivo studies confirmed that SYD985 is significantly more active than T-DM1 against HER2/neu 3 + EOC xenografts. Conclusions SYD985 is a novel ADC with remarkable activity against EOC with strong (3 +) as well as moderate to low (i.e., 2 + and 1 +) HER2/neu expression. SYD985 is more potent than T-DM1 in comparative experiments and unlike T-DM1, it is active against EOC demonstrating moderate/low or heterogeneous HER2/neu expression. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to investigate the impact of BRCA1 protein expression on the patients' outcome of ovarian serous carcinoma, and its correlation with different clinicopathologic features., Methods: Immunohistochemistry with BRCA1 was done for 80 cases of ovarian serous carcinoma that had a positive family history. Correlation with clinico-pathologic variables and patients' outcomes was investigated., Results: BRCA1 expression was detected in 61.2% of the studied cases. A significant relation with patients' age, tumor grade and tumor stage was found (P<0.05). Also, there was a significant decrease in disease free survival (DFS) & overall survival (OS) in the positive BRCA1 group. Metastasis, recurrence, residual disease, and mortality rate showed significantly higher figures in patient with BRCA1 expression (P<0.05)., Conclusion: Positive BRCA1 expression had proven to be associated with advanced stage & grade of tumors, as well as worsened prognostic survival parameters (metastasis, recurrence, residual disease, and mortality) in patients with ovarian serous carcinoma.

Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown. In this study, a set of ovarian tissues including normal fallopian tube, serous borderline tumor, and serous carcinoma were subjected to immunohistochemistry using a specific polyclonal antibody for EphB3. The relationship between EphB3 expression and clinicopathological parameters was statistically analyzed. EphB3 was strongly expressed in all fallopian tube specimens (19/19, 100%). EphB3 was negatively or weekly expressed in 1 of 17 (5.8%) in borderline tumors and 26 of 50 (52.0%) in serous carcinomas, moderately expressed in 7 of 17 (41.2%) in borderline tumors and 14 of 50 (28%) in serous carcinomas, and strongly expressed in 9 17 (52.9%) in borderline tumors and 10 of 50 (20%) in serous carcinomas. EphB3 expression is significantly reduced in serous carcinomas compared with normal fallopian tubes and borderline tumors (p < 0.001). EphB3 expression is negatively associated with histological grade (p < 0.001, rs = −0.613) and FIGO stage (p = 0.001, rs = −0.464) of serous carcinomas. Our results show EphB3 protein lost in ovarian serous carcinoma and is associated with tumor grade and FIGO stage, which indicate EphB3 protein may play a role in carcinogenesis of ovarian serous carcinoma and may be used as a molecular marker for prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Primary ovarian surface epithelial carcinoma (POSEC) is the fourth commonest cancer (5.85%) of women in Malaysia. It is often detected in an advanced stage due to lack of early clinical symptoms. This study was aimed to analyze the immunohistochemical expression of E-cadherin and β-catenin in POSEC and evaluated their association with age, histological subtype, International Federation of Gynecology and Obstetrics (FIGO) stage, tumour grade, capsular invasion and peritoneal deposits. Design: This is a cross sectional (retrospective) study on 88 cases of primary ovarian surface epithelial carcinoma in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. Methods: 88 cases of diagnosed primary ovarian surface epithelial carcinoma (POSEC) were studied. Haematoxylin and eosin stained slides were reviewed. Tissue sections obtained from archived paraffin blocks were stained immunohistochemically for E-cadherin and β-catenin and examined microscopically. Results: In 64.7% of high grade POSEC, E-cadherin and p-catenin immunoexpression were lost (p = 0.026). In 90% of high grade serous carcinoma subtype, both markers were lost (p = 0.004). In early FIGO stage (I and II), 72.2% maintained expression of one of the markers (p = 0.037) but lost both markers in 27.8% of cases. No significant association was observed between E-cadherin and β-catenin expression and age, race, capsular invasion and peritoneal deposit (p > 0.05). Conclusion: Ovarian surface epithelial carcinoma with loss of expression of E-cadherin and p-catenin tend to behave more aggressively and they have higher grade and stage. [ABSTRACT FROM AUTHOR]

Background: Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Disregulation of Eph/ephrin signaling has been implicated in oncogenesis and tumor progression. EphA5 receptor is one of large families of Eph tyrosine kinase receptor and is documented in the development of nervous system. Till now, there is no published data about the role of EphA5 in ovarian epithelial neoplasmas. Methods: This study aims to investigate the expression of EphA5 protein in ovarian serous carcinoma, and its relationship to clinical pathological characteristics. Sixty-one cases of ovarian serous carcinoma, 24 cases of benign ovarian serous tumors, 42 cases of serous borderline tumors and 20 cases of normal fallopian tubes were examined using immunohistochemical staining. The relationship between EphA5 expression and pathological parameters was analyzed. Kaplan-Meier survival function was used to analyze prognosis of patients. Results: Immunostaining analysis demonstrated that the EphA5 protein was highly expressed in 100% (20/20) of normal fallopian tube samples, 100% (24/24) of benign epithelial ovarian tumors, 76% (32/42) of ovarian serous borderline tumors, and 31% (19/61) of ovarian serous carcinomas. Loss of EphA5expression was associated with tumor grade (P < 0.001) and FIGO stage (P = 0.005). The survival analysis showed that patients with negative or weak expression of EphA5 protein had a poor outcome than those with positive expression (P = 0.004). Conclusions: Our results show that EphA5 may be a potential biomarker for distinguishing high-and low-grade ovarian serous carcinoma and a potential prognostic marker. [ABSTRACT FROM AUTHOR]