Accuracy of Intraoperative Frozen Section in the Diagnosis of Ovarian Neoplasms

Objective: The aim of the work is to evaluate the accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms in Zagazig University. Design: A prospective cross sectional cohort study. Method: This study was performed between March 2011 and March 2012, on 50 patients presented with ovarian mass. Gross examination of the tumor removed was done by inspection and palpation. The specimen was then cut with a sharp knife into two halves. The most appropriate area thought to be representative of lesion was chosen. The number of sections frozen was depended on the type and size of the tumor. Seven to eight μm sections were obtained and stained with hematoxylin-eosin. The specimens were then fixed in formalin. Paraffin blocks of the sections were processed in the routine way and sections were stained with hematoxylin and eosin (H and E). The diagnosis obtained by intraoperative frozen section based on cellularity and cell morphology was compared with final histopathological diagnosis in terms of diagnostic sensitivity, to differentiate between benign and malignant lesions. Assessment of the overall accuracy of the intraoperative diagnosis was classified as concordant or discordant. Results: There was no statisticaly significant differencre in the studied patients as regard the clinical data, macroscopic and intraoperative picture, while there was statisticaly significat association as regard the laterality of the ovarian masses. The validity of frozen section in the diagnosis of benign tumour was 100% with 100% accuracy, specificity, positive predictive value, negative predictive value, while sensitivity & negative prediction for borderline tumour and specificity & positive prediction of malignant tumour were 100%, specifecity for borderline tumours was 95% while the positive predictive value was 33.3% with 96% accuracy for both malignant and borderline tumours. Conclusion: Intraoperative frozen section is accurate for rapid diagnosis of ovarian tumors. It can help surgeons avoid under-treatment or overtreatment of patients. Our study was designed prospectively using a small number of patients. The door is open to larger studies using a larger number of patients to be performed in order to substantiate our results.

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.

TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Expression and significance of tumor suppressor gene p16 in human ovarian neoplasm

To observe the relationship between tumor suppressor gene p16 expression and ovarian cancer occurrence and development. Metbods: Using ABC immunohistochemistry method, we investigated the expression of p16 in 72 cases of ovarian neoplasm. Results: The positive rates of p16 in malignant, benign, borderline tumors and normal ovarian tissue were 7. 89%, 60.00%, 66. 67% and 83. 33%, respectively (P<0.01). In the cases whose tumors were more malignant and poorly differentiated, and who relapsed and died, the positive stainings were not discovered. Conclusiou: p16 is well related with the occurrence and development of malignant ovarian tumor.

The diagnostic value of multiple tumor markers in malignantovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

The Relationship between Methylation and Expression Defect of Tumor Suppressor Gene p16INK4A in Epithelial Ovarian Cancer

Objective： To evaluate the expression of p16INK4A gene in ovarian cancer and analyze the relation between this alteration and the promoter methylation of p16INK4A DNA. Methods： Seven ovarian cancer cell lines and eighteen ovarian cancer specimens were selected for the study. Genomic DNA and RNA were extracted from fresh tissues and cell lines, DNA was treated with sodium bisulfite and then analyzed with methylation-specific PCR （MSP） to detect p16INK4A methylation. The expression of p16INK4A mRNA was detected by reverse transcription-polymerase chain reaction （RT-PCR）. In addition, the proliferation of methylated cell lines before and after treatment of demethylating agent 5-Aza-2＇-deoxycytidine （5-ADC） was examined with 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay in vivo. Results： Compared with the control, the expression of p16INK4A mRNA decreased significantly or absolutely defaulted in 10 of 18 （55.56%） ovarian cancer specimens and 71.4% （5/7） ovarian cancer cell lines （P〈0.05）, and the expression of p16INK4A protein also decreased （P〈0.05）. The decrease of p16INK4A was due, in part, to p16INK4A methylation, which was found in the first exon of three cell lines and six ovarian cancer specimens and the rate was 42.86% and 33.33% in ovarian cancer cell lines and specimens respectively. All the methylated cells and tissues showed expression defect of p16INK4A, but the treatment of 5-ADC reactivated the expression of p16INK4A in methylated cells and decreased the proliferation of tumor cells in vitro and in vivo. Conclusion： The expression defect of p16INK4A gene possibly has an important role in the development of ovarian cancer, and this alteration is due, in part, to the methylation of the first exon in p16INK4A.

EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENEmRNA ON TUMORIGENESIS AND PROGRESSION OFEPITHELIAL OVARIAN CANCER

Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

Relationship between the Expression of Connexin43 and Bystander Effect of Suicide Gene Therapy in Ovarian Cancer

The relationship of connexin43 (Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro was explored and the effect of all-trans retinoic acid (RA) on the expression of Cx43 and bystander effect investigated. The Cx43 expression was detected by flowcytometry, Western blot, and immunofluorescence in two ovarian tumor cell lines OVCAR3, CaOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than that in CaOV3 (P<0.05). The expression of Cx43 was detected in OVCAR3 by flowcytometry and Western blot, but it could not be detected in CaOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluoresence staining showed that Cx43 protein of OVCAR3 was located on membrane surface, whereas CaOV3 in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be enhanced by RA in ovarian cancer.

Cloning of WWOX Gene and Its Growth-inhibiting Effects on Ovarian Cancer Cells

The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reaction(RT-PCR) and immunoblotting.The growth activities of cancer cells were detected by Trypan blue staining.The clone formation assay in soft agar was employed to observe the proliferation of the cancer cells.Apoptosis was examined by DNA ladder and acridine orange-ethidium bromide fluorescent staining.The results showed that 72 h after WWOX gene transfection,the WWOX expression was increased significantly(P<0.01).The growth of ovarian cancer cells was decreased by 16.41% to 38.49%(P<0.01).The clone formation abilities were reduced(P<0.01).Some cancer cells presented the characteristic morphological changes of apoptosis with obvious ladder bands on electrophoresis.The apoptosis rate was(20.7±6.0)%(P<0.01).It was concluded that over-expression of WWOX gene could induce apoptosis and inhibit the growth of ovarian cancer cells,which might be potentially useful in the gene therapy of ovarian cancers.

Establishment and validation of a nomogram to predict the risk of ovarian metastasis in gastric cancer: Based on a large cohort

BACKGROUND Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer.The pathogenesis of ovarian metastasis is incompletely understood,and the treatment options are controversial.Few studies have predicted the risk of ovarian metastasis.It is not clear which type of gastric cancer is more likely to metastasize to the ovary.A prediction model based on risk factors is needed to improve the rate of detection and diagnosis.AIM To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features.METHODS A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center,and patients with distant metastasis other than ovary and peritoneum metastasis were excluded.Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression.Independent risk factors were chosen to construct a nomogram which received internal validation.RESULTS Ovarian metastasis occurred in 83 of 1696 female patients.Univariate analysis showed that age,Lauren type,whether the primary lesion contained signet-ring cells,vascular tumor emboli,T stage,N stage,the expression of estrogen receptor,the expression of progesterone receptor,serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer(all P<0.05).Multivariate analysis showed that age<50 years,Lauren typing of non-intestinal,gastric cancer lesions containing signet-ring cell components,N stage>N2,positive expression of estrogen receptor,serum carbohydrate antigen 125>35 U/mL,and a neutrophil-to-lymphocyte ratio>2.16 were independent risk factors(all P<0.05).The independent risk factors were constructed into a nomogram model using R language software.The consistency index after continuous correction was 0.840[95%confidence interval:(0.7740.906)].After the internal self-sampling(Bootstrap)test,the calibration curve of the model was obtained with an average absolute error of 0.007.The receiver operating characteristic curve of the obtained model was drawn.The area under the curve was 0.867,the maximal Youden index was 0.613,the corresponding sensitivity was 0.794,and the specificity was 0.819.CONCLUSION The nomogram model performed well in the prediction of ovarian metastasis.Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination,to ensure early detection and treatment.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma

BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

SCREENING OF DRUG RESISTANCE-RELATED GENES FROM HUMAN OVARIAN CANCER CELL LINE OC3/ADR BY DD-PCR

Objective: To screen novel genes related to adriamycin (Adr) resistance from human ovarian cancer resistance cell line OC3/Adr. Methods: Multidrug resistant ovarian cancer cell line OC3/Adr was induced by intermittent treatment of the human parent cell line OC3 with high concentration Adr. The difference of gene expression was screened by using different display analysis to the acquired Adr-resistance subline OC3/Adr and its parent cell line OC3. Results: OC3/Adr cell line was obtained which was more resistance to Adr than the parent cell line OC3 with the resistance index (RI) of 15.4. The OC3/Adr cell line also showed cross-resistance to other anti-cancer drugs (VP16, CDDP,5FU). It grew slowly and exhibited changes of cell cycle. A number of differentially expressed ESTs (Expressed Sequence Tags, ESTs) were identified at mRNA level between the OC3/Adr and OC3. Four of 18 different ESTs were sequenced. The 431/432 base pair S1 was homologous to human sperm zona pellucida binding protein, while the other two ESTs, S3 and S4, were new gene segments, which were registered to GenBank with the number of AF 117656 and AF 126507 respectively. Particularly, the expression of S2 sequence increased in all the drug-resistance cell lines and S3 sequence overexpressed in human ovarian cancer tissues as compared with benign ovarian tumors. Conclusion: Drug resistance induced by Adr in ovarian cancer OC3/Adr is involved with changes of multiple gene expressions.

PROLIFERATING CELL NUCLEAR ANTIGEN(PCNA) IN OVARIAN CARCINOMA AND ITS RELATION TO LYMPH NODE METASTASIS AND PROGNOSIS

Objective: To investigate expression of proliferating cell nuclear antigen (PCNA) in ovarian epithelial cancer and its relation to lymph node metastasis, outcome of second look laparotomy (SLL) and prognosis Methods: Monoclonal antibody PC10 was used to stain PCNA in archival paraffin embedded tissues Results: PC10 immunostaining was performed successfully in all 74 primary and 31 intraperitoneal metastatic tumors The expression levels of PCNA were significantly increased in 31 metastatic tumors compared with their primary tumor from the same patients (7 94 vs 6 89, P=0 042) The expression levels was more elevated in bilateral than in unilateral ovarian cancer, but it was not associated with lymph node metastasis, clinical stage, histological grade and subtype In 28 patients with stage III ovarian cancer undergone SLL, the mean immunoreactive score (IRS) of PCNA of the primary tumor was significantly higher in patients with negative SLL than in those with positive SLL (7 59 vs 6 10, P =0 03) Since chemotherapy was performed following surgical debulking, negative SLL more frequently seen in patients with high PCNA expression might suggest better chemotherapeutic sensitivity due to higher proliferation fraction of tumor cell Univariate analysis of survival indicated that the overall survival was inversely associated with the level of PCNA expression, while multivariate analysis with Cox's model showed that independent prognostic factors were the residual tumor after primary debulking ( P<0 001 ) and clinical stage ( P <0 05), followed by PCNA expression( P =0 09) Conclusion: The expression of PCNA may beuseful in predicting the patients' prognosis, but is not correlated with lymph node metastasis

Inhibitory effect of medroxyprogesterone acetate on malignant growth of ovarian cancer 3AO cell line

Ovarian cancer 3AO cell line was treated with medroxyprogesterone acetate in vitro. The results showed that medroxyprogesterone acetate inhibited the growth of 3AO cell line. Three days after treatment, significant decrease in colony formation on the soft agar medium and subcutaneous transplant tumor formation in the nude mice were observed, and at the same time, C-erbB_2 expression in part of the 3AO cells decreased as analyzed by flow cytometry and immunohistochemical staining. Electron microscopic examination revealed certain degree of degeneration in part of the cells.

Epithelial ovarian carcinoma in women aged below 30 years

Objective:To study the manifestation,pathohistologic type,stage of disease,treatment andoutcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods:The 21 cases of epithelial ovarian carcinoma in women aged below 30 years betweenJan,1986 and Mar,2002 were analyzed retrospectively.Results:The median age at the time of diagnosis was 24 years(range,16-29 years).All car-cinomas occurred after menarche.The most common symptoms were abdominal pain(50%),fol-lowed by tympanites(25%)and menstrual disorders(19%).The initial diagnosis was usuallymade by physical examination,ultrasonography and serum CA125.The mean maximal tumor di-ameter was 17.6 cm.Ten patients had Stage Ⅰ disease(5 Ⅰa,5 Ⅰc),five had Stage Ⅲ disease,andthe other six were unknown during staging operation.There were nine mucinous tumors,six se-rous tumors.Most tumors were well-differentiated and classified as Grade1 in 11 cases,Grade2 in2 cases,Grade3 in 2 cases,unknown in 6 cases.Optimal and suboptimal cytoreduction wasachieved in 14 patients in primary treatment and 5 in recurrent treatment.8 patients were treatedwith conservative surgery.18 patients were treated with chemotherapy and 7 patients had experi-enced six or more than six courses of chemotherapy.The median follow-up was 50 months(range,2-192 months).There were 6 deaths,2 alive with tumor,11 alive without the disease,2losing follow-up.The 3-year survival rate was 89%,and 5-year survival rate was 76%.Conclusion:Young patients with epithelial ovarian carcinoma appeared to have a less aggres-sive form of the disease and a more favorable prognosis.

EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A

Objective:Histone modification has a significant effect on gene expression.Enhancer of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme.The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors.The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.Methods:In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues,we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice.Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine(m6A)levels were modified.Results:EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues.Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo.M6a regulation altered the effect of EZH2 on anoikis resistance.Conclusion:Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification.Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

Human Epididymis Protein-4 Gene Expression as a Biomarker in Patients with Ovarian Cancer in Iran

Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.

EXPRESSION AND SIGNIFICANCE OF BASIC FIBROBLAST GWOWTH FACTOR AND FIBROBLAST GROWTH FACTOR RECEPTOR-1 IN OVARIAN EPITHELIAL NEOPLASM

Objective To study the relevance of expression of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor 1 (FGFR 1) and carcinogenesis and progression of ovarian epithelial neoplasm. Methods Ten cases of normal ovarian tissues and 75 cases of ovarian epithelial neoplasm tissues were detected by immunohistochemical methods: S P for bFGF, FGFR 1,double immunohistochemistry Lab SA for Ki 67 antigen and bFGF. Results The expression level of bFGF, FGFR 1in ovarian epithelium and ovarian epithelial neoplasm showed a step wise increase in the following order:normal <benign <borderline <malignant; The expression level and intensity of bFGF and FGFR 1 were increased with the decrease of differentiation degree and increase of clinical stage in ovarian carcinoma; There was no statistical difference between the expression of bFGF, FGFR 1 in serous cystadenocarcinoma and that of mucinous cystadenocarcinoma; The expression of bFGF was correlated with that of FGFR 1 in neoplastic tissues; There were positive expression rates of bFGF and Ki 67 antigen in ovarian epithelial neoplasm. Conclusion As an important proliferative factor, bFGF plays an important role in carcinogenisis and progression of ovarian epithelial neoplasm.

WHAT SHOULD BE KEPT IN MIND FOR MANAGEMENT OF THE TOXIC SIDE-EFFECTS INDUCED BY POSTOPERATIVE CHEMO-AND RADIOTHERAPY FOR OVARIAN TUMOR?

Ovarian tumor may occur in women ofany age, but mostly seen in women duringtheir child-bearing period. The disease shouldbe treated mainly by surgical operation,supplemented by radiotherapy and chemo-therapy. However, the above therapies maycause a series of toxic side-effects, such asalopecia, diarrhea, edema, anorexia, nausea,dry mouth, spontaneous perspiration, headache,