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

Humans ; Breast/pathology* ; Cystadenocarcinoma/pathology* ; Cystadenocarcinoma, Mucinous/pathology* ; Female

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

OBJECTIVE: Ovarian needle aspiration and biopsy (ONAB) may be employed for pretreatment diagnosis of ovarian malignancies or intraoperatively to facilitate removal of ovarian masses. However, there is reluctance to utilize this procedure due to potential cyst rupture or seeding of malignant cells. The objective of this study was to examine the efficacy of ONAB over a 13-year period at our institution. METHODS: Between 2000 and 2013, all ONAB specimens were identified from the Queen's Medical Center Pathology Department database. All cytologic specimens were reviewed and correlated with histopathologic findings. A retrospective chart review was conducted to retrieve data on clinical course and treatment. RESULTS: This study identified 144 cases of ovarian masses sampled by aspiration or needle biopsy between 2000 and 2013. Ninety-two (64%) cases had corresponding histopathology, 84 (91%) of which were obtained concomitantly. On histology, 12 (13%) cases were malignant and 80 (87%) benign. Three false negative cases were noted; 2 serous borderline tumors and 1 mucinous cystadenocarcinoma. These were sampling errors; no diagnostic tumor cells were present in the aspirates. Sensitivity and specificity of ONAB in the detection of malignancy were 75% and 100%, respectively. The positive and negative predictive values were 100% and 96%, respectively. CONCLUSION: ONAB represents a valuable tool in the diagnosis of malignancy and treatment of ovarian masses. In our study, it was highly specific, with excellent positive and negative predictive value.
Biopsy ; Biopsy, Needle ; Cystadenocarcinoma, Mucinous ; Diagnosis* ; Needles* ; Ovarian Neoplasms ; Pathology ; Retrospective Studies ; Rupture ; Selection Bias ; Sensitivity and Specificity

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

OBJECTIVETo study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer.

METHODSThe immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored.

RESULTSThe P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors.

CONCLUSIONThe P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.

CA-125 Antigen ; blood ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Membrane Proteins ; blood ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Tumor Suppressor Protein p53 ; metabolism

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

Carcinoma, Renal Cell ; secondary ; Cystadenocarcinoma, Serous ; pathology ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; pathology ; Ovarian Neoplasms ; pathology

OBJECTIVETo assess clinical and pathological features of ovarian transitional cell tumors.

METHODSFourteen cases of ovarian transitional cell carcinoma (TCC) were selected and investigated for their clinical and pathological features. Their immunohistochemical profiles were compared with 12 cases of serous adenocarcinoma (SC) admixed with TCC and 4 cases of EC admixed with TCC 20 cases of pure high-grade serous adenocarcinoma (HG-SC), 15 cases of endometrioid adenocarcinoma (EC), 6 cases of Brenner tumor (BT, 2 cases of malignant BT and 4 cases of benign BT).

RESULTSThe patients' age ranged from 36-63 years (mean, 56 years). All cases underwent surgery and postoperative chemotherapy with TP or CAP program. Clinical follow-up was available in 9 cases, of which 2 patients died. Histologically, all cases showed features of transitional cell carcinoma without BT component. Immunohistochemically, 13 of 14 TCCs were positive for WT-1 and all were positive for CK7, ER, PR and CA125, but negative for Uroplakin III and CK20.Similar immunohistochemical staining patterns were seen in SC admixed with TCC and pure HG-SC. Percentage of the 14 TCC cases were also diffusely positive for BRCA1. All SCs admixed with TCC and pure HG-SCs were diffusely or heterogeneously positive for WT-1, with a sharp contrast and mottled distribution pattern in the heterogeneous cases. All TCCs were diffusely and strongly positive for p53, while 16 of 20 cases of pure HG-SC were positive. The positive ratio of p53 in SCs admixed with TCC cases was 11/12.WT-1 expression in TCCs was significantly higher than BTs, ECs and ECs admixed with TCC (P < 0.01), while no obvious difference was seen when compared with SCs admixed with TCC and pure HG-SCs.SCs admixed with TCC, TCCs and EC were positive for BRCA1 except pure ECs and BTs. The positive rate of Ki-67 of BTs was low, while it was higher in TCCs, SCs admixed with TCC and pure HG-SCs. Only BTs expressed Uroplakin III.

CONCLUSIONSOvarian TCC has characteristic morphological and immunohistochemical features, similar to SC but different from BT. Therefore, TCC should be considered as a morphological variant of HG-SC.

Adult ; Brenner Tumor ; metabolism ; pathology ; CA-125 Antigen ; metabolism ; Carcinoma, Endometrioid ; pathology ; Carcinoma, Transitional Cell ; pathology ; Cystadenocarcinoma, Serous ; pathology ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasms, Glandular and Epithelial ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Uroplakin III ; metabolism