Objective To investigate the expression of long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and its relationship with immune infiltration in ovarian serous cystadenocarcinoma (OSC), and to determine its prognostic role in OSC. Methods The Cancer Genome Atlas (TCGA) database was utilized to retrieve the expression of USP30-AS1 and clinical information of 384 OSC patients. Wilcoxon rank-sum test was employed to compare the expression of USP30-AS1 between OSC and normal ovarian tissues. Logistic regression analysis was conducted to assess the relationship between clinical pathological features and USP30-AS1. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate enrichment pathways and functions and quantify the degree of immune cell infiltration in USP30-AS1. Based on the expression level of long non-coding RNA (lncRNA) USP30-AS1, the samples were divided into high and low expression groups according to the expression mean. Log-rank tests, univariate and multivariate proportional hazards model (Cox) were used to compare prognostic differences between different USP30-AS1 expression groups. The impact of lncRNA USP30-AS1 expression on other genomic analyses was also analyzed. Results High expression of USP30-AS1 was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) stage of the tumor. Multivariate survival analysis indicated that USP30-AS1 expression level served as an independent prognostic marker for OSC. GSEA data showed that high expression of USP30-AS1 might activate programmed death 1 (PD-1) signaling pathway, cytotoxic T lymphocyte-associated protein 4 (CTLA4) pathway, B-cell receptor signaling pathway, cell apoptosis, fibroblast growth factor receptor (FGFR) signaling pathway, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. The expression of USP30-AS1 was negatively correlated with immune cell infiltration, including B cells, CD4⁺ T cells, dendritic cells, CD8⁺ T cells, and neutrophils. Conclusion USP30-AS1 may be used as a prognostic molecular marker for OSC.
Female ; Humans ; Pregnancy ; CD8-Positive T-Lymphocytes ; Computational Biology ; Cystadenocarcinoma, Serous/genetics* ; RNA, Antisense ; RNA, Long Noncoding/genetics* ; Ubiquitin-Specific Proteases/genetics*

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.
Female ; Humans ; Carcinoembryonic Antigen ; Ascites ; CA-19-9 Antigen ; Mesothelioma, Malignant/diagnosis* ; Hyperplasia ; Adenocarcinoma/pathology* ; Cystadenocarcinoma, Serous/diagnosis* ; Biomarkers, Tumor ; Carcinoma, Ovarian Epithelial ; Diagnosis, Differential ; Ovarian Neoplasms/pathology* ; Carbohydrates

To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery. A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (<0.05). The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.
Cystadenocarcinoma, Serous/surgery* ; Humans ; Neoplasm Staging ; Nomograms ; Prognosis ; ROC Curve ; Retrospective Studies ; SEER Program ; Survival Rate

OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.
Carcinogenesis ; Cystadenocarcinoma, Serous ; Fallopian Tube Neoplasms ; Fallopian Tubes ; Female ; Humans ; Incidence ; Multivariate Analysis ; Obstetric Surgical Procedures ; Ovarian Neoplasms ; Parity ; Pregnancy ; Pregnant Women ; Prospective Studies ; Risk Reduction Behavior ; Tumor Suppressor Protein p53

Schistosomiasis has been established as a causative factor in urinary bladder, liver, colorectal and cervical cancer. However, its role in ovarian malignancy has not been described. With the premise that long-standing inflammation secondary to chronic infection predisposes to cancer by promoting an environment that cultivates genomic lesions and tumor initiation, we are left with an open question: Does chronic infection with schistosomiasis also predispose to ovarian cancer? In this paper, we presented a case of a 54-year-old diagnosed with high grade serous carcinoma of the ovary and fallopian tube with a history of chronic infection with Schistosomiasis. In this case, the infection caused neoplastic lesions in the right fallopian tube with subsequent seeding of malignant cells to the right ovary, indirectly causing the high grade serous ovarian carcinoma of the patient.
Fallopian Tubes ; Cystadenocarcinoma, Serous ; Ovarian Neoplasms ; Schistosomiasis

BACKGROUNDOvarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas.

METHODSThe PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed.

RESULTSIn high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P< 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P< 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis.

CONCLUSIONSAbnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting common molecular pathways. Decreased PHLPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Forkhead Box Protein O3 ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Nuclear Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Phosphoprotein Phosphatases ; metabolism ; Prognosis ; Rad51 Recombinase ; metabolism

No abstract available.
Chemotherapy, Adjuvant ; Combined Modality Therapy ; *Cystadenocarcinoma, Serous ; Humans ; Neoplasm Staging ; *Uterine Neoplasms

PURPOSE: Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years. MATERIALS AND METHODS: Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool. RESULTS: We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI. CONCLUSION: The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI.
Cystadenocarcinoma, Serous/*genetics/*mortality/pathology ; Databases, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Microarray Analysis ; Middle Aged ; Ovarian Neoplasms/*genetics/*mortality/pathology ; Prognosis ; Regression Analysis ; Retrospective Studies ; Survival Rate

OBJECTIVE: To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012. METHODS: Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (<40, 40 to 59, and >59 years), and age-specific incidence rates were compared. RESULTS: Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, -1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999. CONCLUSION: The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.
Adenocarcinoma, Clear Cell/epidemiology/pathology ; Adenocarcinoma, Mucinous/epidemiology/pathology ; Adult ; Age Distribution ; Aged ; Carcinoma, Endometrioid/epidemiology/pathology ; Cystadenocarcinoma, Serous/epidemiology/pathology ; Databases, Factual ; Female ; Humans ; Incidence ; Middle Aged ; Neoplasms, Glandular and Epithelial/*epidemiology/pathology ; Ovarian Neoplasms/*epidemiology/pathology ; Registries ; Republic of Korea/epidemiology

OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and < or = median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/genetics ; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology ; Ovarian Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; Tumor Cells, Cultured