OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; CA-125 Antigen/*blood/metabolism ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/*blood/*drug therapy/mortality ; Ovarian Neoplasms/*blood/*drug therapy/mortality ; Prognosis ; Regression Analysis

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

OBJECTIVETo investigate the correlations among OCT4, Notch1 and DLL4 and their association with the clinicopathological features of patients with epithelial ovarian cancer (EOC).

METHODSA total of 207 specimens of EOC and 65 specimens of benign ovarian epithelial tumor tissues were examined for expressions of OCT4, Notch1 and DLL4 proteins using immunohistochemistry.

RESULTSThe positivity rates of OCT4, Notch1 and DLL4 in EOC tissues were 60.0%, 61.8% and 60.9%, respectively, significantly higher than the rates in benign epithelial tumor tissues (9.2%, 6.2%, and 0, respectively; P<0.05). The expressions of OCT4, Notch1 and DLL4 in EOC were significantly correlated with tumor differentiation, FIGO stage, and lymph node metastasis (P<0.05). DLL4 was positively correlated with OCT4 and Notch1 expressions (r=0.758 and 0.704, respectively, P<0.001), and the latter two were also positively correlated (r=0.645, P<0.001). Overexpressions of OCT4, Notch1 and DLL4 were associated with a poor prognosis, and the survival rate was significantly lower in patients positive for OCT4, Notch1, and DLL4 than in the negative patients (P<0.05). FIGO stage and expressions of OCT4 and DLL4 were independent prognostic factors of EOC (P<0.05).

CONCLUSIONThe expressions of OCT4, Notch1 and DLL4 are correlated with the differentiation, lymph node metastasis, clinical stage and prognosis of EOC. Combined detection of the 3 proteins has an important value in predicting the progression and prognosis of EOC.

Disease Progression ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; metabolism ; Lymphatic Metastasis ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Octamer Transcription Factor-3 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Receptor, Notch1 ; metabolism ; Survival Rate

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.
Algorithms ; Area Under Curve ; Biomarkers, Tumor/blood ; CA-125 Antigen/*blood ; Case-Control Studies ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial/*blood/*diagnosis ; Ovarian Neoplasms/*blood/*diagnosis ; Predictive Value of Tests ; Prospective Studies ; Proteins/*metabolism ; ROC Curve ; Reference Values ; Republic of Korea

Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.
Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Cell Cycle Proteins/analysis/*genetics ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Glandular and Epithelial/diagnosis/*genetics/*pathology ; Nuclear Proteins/analysis/*genetics ; Ovarian Neoplasms/diagnosis/*genetics/*pathology ; Ovary/metabolism/*pathology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Young Adult

OBJECTIVETo investigate the expression patterns of ZEB2 and C-myc in epithelial ovarian cancer (EOC) and the associations between their expressions and the pathological features of EOC.

METHODSThe expressions of ZEB2 and C-myc proteins were detected immunohistochemically in 191 cervical cancer tissues and 13 normal ovarian tissues. The relationship between ZEB2 and C-myc protein expressions and the clinicopathological features of EOC was evaluated.

RESULTSZEB2 positive expression ratea in EOC tissues and normal ovarian tissues were 49.2% (94/191) and 30.8% (4/13), respectively (P=0.007), and C-myc positive expression rates in the two tissues were 53.9% (103/191) and 15.4% (2/13), respectively (P=0.001). A high expression of ZEB2 was positively correlated with the pathological type of the tumor (P=0.003), FIGO stage (P=0.028), T stage (P=0.002), and N stage (P=0.04), and a high expression of C-myc was positively correlated with FIGO stage (P=0.035), histological grade (P=0.039), and T stage (P=0.002). C-myc and ZEB2 expressions were positively correlated in EOC (P<0.001), and their co-expression in EOC was significantly correlated with T stage (R=0.358, P<0.001) and FIGO stage (P=0.008).

CONCLUSIONZEB2 and C-myc can promote the progression, invasion and metastasis of EOC, and their combined detection may assist in early diagnosis of EOC.

Disease Progression ; Female ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Neoplasms, Glandular and Epithelial ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Zinc Finger E-box Binding Homeobox 2

OBJECTIVETo investigate the expression of microRNA-100(miR-100) and the relationship with cisplatin resistance in human ovarian epithelial cancer SKOV3/DDP cells.

METHODSThe SKOV3/DDP cells were transfected with the mimics or inhibitor of miR-100 or negative control RNA (NC) or inhibitor negative control RNA (inhibitor NC) by lipofectamine 2000. The experiment was divided into six groups: SKOV3 group, SKOV3/DDP group, miR-100 mimices group, NC group, miR-100 inhibitor group and inhibitor NC group. The expression of miR-100 and the cisplatin IC50 were measured by real-time PCR and CCK8 assay respectively.

RESULTS(1)The cisplatin resistance index of SKOV3/DDP was 2.23; (2)The express level of miR-100 in SKOV3/DDP cells was significantly lower than that in SKOV3 cells (P<0.001); (3)After transfected with miR-100 mimics, SKOV3/DDP cells showed that the level of miR-100 was 38.29 times higher than that in the NC group(P<0.01). The cisplatin IC50 of miR-100 mimices group was significantly lower than that in the NC group (P<0.001); (4) After transfected with miR-100 inhibitor, the level of miR-100 0f SKOV3/DDP was decreased by 97.7%. The cisplatin IC50 of miR-100 inhibitor group was significantly increased as compared with that in the inhibitor NC group (P<0.001).

CONCLUSIONThe expression of miR-100 is downregulated in SKOV3/DDP cells. Overexpressing miR-100 may effectively increase the sensitivity to cisplatin of human ovarian epithelial cancer SKOV3/DDP cells and may reverse cisplatin-resistance of EOC (epithelial ovarian cancer).

Antineoplastic Agents ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Down-Regulation ; Drug Resistance, Neoplasm ; Female ; Humans ; MicroRNAs ; metabolism ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Real-Time Polymerase Chain Reaction ; Transfection

OBJECTIVETo explore expressions of CD133, E-cadherin and Snail in human epithelial ovarian cancer (EOC) and elucidate their relationship with the clinicopathologic features and prognosis of the patients.

METHODSThe expression of CD133, E-cadherin and Snail were detected by immunohistochemical staining in 150 specimens of EOC and 50 specimens of benign ovarian epithelial tumor tissues.

RESULTSThe positivity rates of CD133, E-cadherin and Snail protein in EOC were 58.7%, 60.7% and 32.7%, respectively, significantly different from the rates in benign epithelial tumor tissues (10%, 8.0%, and 70%, respectively; P<0.05). The expressions of CD133, E-cadherin and Snail in EOC were significantly correlated with abdominal organ and lymphnode metastases and FIGO stage (P<0.01). E-cadherin expression was inversely correlated with Snail and CD133 expression (r=-0.545 and -0.570, P<0.01), and the latter two were positively correlated (r=0.599, P<0.01). Overexpressions of CD133 and Snail and a decreased expression of E-cadherin were all related to a poor prognosis of the patients (P<0.05). FIGO stage and expressions of CD133, E-cadherin and Snail were all independent prognostic factors of EOC (P<0.05).

CONCLUSIONThe expressions of CD133, E-cadherin and Snail are related to lymph node metastasis, clinical stage, and prognosis of EOC. Combined detection of these indexes provides important evidence for predicting the progression and prognosis of EOC.

AC133 Antigen ; Antigens, CD ; metabolism ; Cadherins ; metabolism ; Disease Progression ; Female ; Glycoproteins ; metabolism ; Humans ; Lymphatic Metastasis ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Peptides ; metabolism ; Prognosis ; Snail Family Transcription Factors ; Transcription Factors ; metabolism