The Inhibitory Effect of KIAA1456 on the Proliferation and Metastasis of Epithelial Ovarian Cancer Through SSX1 and AKT Signaling Pathway

Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian tumours. In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of epithelial ovarian cancer were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in epithelial ovarian tumours and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with epithelial ovarian cancer was analysed with Kaplan–Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with a lentivirus. The anticancer activity of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT signalling pathway were differentially expressed in KIAA1456-overexpressing and control cells. Therefore, the biological function of HO8910PM cotransfected with KIAA1456- and SSX1-overexpressing cells was detected to validate the rescue effect of SSX1. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis, including p-AKT, PCNA, MMP9, CyclinD1 and Bcl-2, were detected by Western blot analysis.Results: KIAA1456 expression was lower in epithelial ovarian tumours than in normal ovarian tissues. Its expression level negatively correlated with pathological grade. Pearson’s correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. By contrast, the silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. Mechanistically, the overexpression of KIAA1456 inhibited SSX1 expression and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT signalling pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. Similarly, the silencing of KIAA1456 resulted in the opposite behaviour. Finally, SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for epithelial ovarian cancers.

Galectin-1 as a predictive biomarker in ovarian cancer

Aim There is an urgent need to set up a useful biomarker for ovarian cancer. Galectin-1 is a promising carbohydrate-binding protein which plays a remarkable role in various malignancies yet its clinical significance is questionable. In this study, we have tested the clinical implications of serum Galectin-1 levels in patients with ovarian tumours. Main methods Serum Galectin-1 levels were quantified in 84 newly diagnosed ovarian tumour patients and 20 healthy controls by Enzyme Linked Immuno Sorbent Assay during the course of the disease. Therefore the samples were taken at diagnosis, after surgery and after chemotherapy. Key findings The Galectin-1 levels were found to be associated with various variables of Ovarian Cancer patients. The levels were found to be prominently high in postmenopausal patients. Galectin-1 levels were raised in epithelial ovarian tumours with significantly high levels in serous subtype. A decrease in Galectin-1 levels post-surgical intervention and after receiving chemotherapy was found. Galectin-1 levels evidently distinguished between normal, benign, malignant and metastatic cases as compared to CA125 levels. Galectin-1 demonstrated to be a better biomarker than CA125 according to the Receiver Operating Characteristic (ROC) curve analysis. Significance The study emphasizes that serum Galectin-1 may serve as a better surrogate biomarker in Ovarian Cancer for early detection, discriminating between malignant and benign abdominal masses and monitoring the progression of the disease and response to treatment.

CD44 and E-Cadherin Expression in Primary Epithelial Tumours of Ovary and Comparison with Histological Type and Tumour Differentiation - A Cross-Sectional Study from Thrissur, Kerala

BACKGROUND Ovarian tumours are the common cause of morbidity and mortality in women worldwide. Primary epithelial ovarian tumours comprise the majority. Cluster differentiation 44 (CD-44) is a trans-membrane glycoprotein which plays a role in cell- cell interaction, adhesion and migration, leading to the progression and metastasis of tumour. E-cadherin is another cell adhesion molecule which plays an important role in neoplastic progression. So, it is necessary to find out the relationship of CD-44 and E-cadherin expression with histological types and tumour differentiation, which might predict the prognosis. The present study was undertaken to assess the pattern of expression of CD-44 and E-cadherin in primary epithelial tumours of ovary and to determine the relationship between their expression with age, histological type and tumour differentiation. METHODS This is a cross-sectional study conducted in the Department of Pathology, Government Medical College, Thrissur; a tertiary care institution. Histological types and tumour differentiation for each case was determined from haematoxylin and eosin sections. Immunohistochemical stain for CD-44 and E-cadherin was done. Pattern of expression was studied and a semi quantitative score was calculated. Expression of both markers was then compared with the age, histological type and tumour differentiation. RESULTS Out of 57 cases studied, majority of the patients had serous (21 cases) or mucinous tumours (20 cases). The mean age group was 54.5 years. CD-44 expression was significantly correlated with tumour differentiation but there was no correlation found with age and histological type. In E-cadherin expression, there was no correlation with age, histological type and tumour differentiation. CONCLUSIONS For primary epithelial tumours, expression of CD-44 could be an indicator for tumour progression, invasiveness or distant metastasis. Poorly differentiated tumours with increased expression may be helpful in predicting disease progression. Target therapy can be employed in such cases. In case of E-cadherin which is said to be a prognostic marker, more studies help in bridging the gap between prognosis and outcome. KEYWORDS CD-44, E-cadherin, Immunohistochemistry, Epithelial Ovarian Tumours f

The treatment approach of a 12 kg giant ovarian mucinous cystadenoma in a 13-year-old: a case report

Epithelial ovarian tumours are rare in the adolescent age group, accounting for less than 15% of overall ovarian malignancy. Of this, one-fourth of them are mucinous in nature. Mucinous cystadenomas, being precursors of borderline and invasive ovarian tumours, can reach to size as large as 15-30 cm in diameter without having malignant potential. Also, intraoperative management of such large abdominal mass can be challenging. We present a case of a giant unilateral 12 kg mucinous cystadenoma in a 13-year-old young girl, that grew over a period of 1 year. She underwent left salpingo-oophorectomy after decompression of the mass without any complications.

Non-Epithelial Ovarian Cancer, an Experience From Qatar

Background: Nonepithelial Ovarian cancers constitute about 10 % of all ovarian cancers. They are divided into Sex-cord stromal tumours (SCST) and Germ cell tumours (GCT). The Aim is to report the experience at National Centre for Cancer Care and Research (NCCCR) in Qatar. Method: This is a retrospective study reviewing records of all patients over 7 years who presented with a histopathologically diagnosed ovarian SCST and GCT at NCCCR between January 2010 and December 2016. Results: 25 women with Non-Epithelial Ovarian Tumours were identified. 13 women were diagnosed with Ovarian SCST. Median age at presentation was 43 years (Range 16-58). 12 patients had stage I and one patient had Stage III. Four patients had recurrence. The 5 years Overall Survival (OS) was 100% and the 5 years Event Free Survival (EFS) was 69% with P value of 0.02. GCT was diagnosed in 12 women. The median age at presentation was 24 years. (Range 16 – 44). Seven patients (59 %) had teratoma, four patients (33 %) had Dysgerminoma and one patient had Yolk sac tumour (8 %). There was one recurrence. 5 years OS was 100 % and 5 years EFS was 83 % with P value of 0.14. Conclusions: Non-Epithelial ovarian tumours are diagnosed relatively at an early stage and have very good prognosis even if they recur. Survival in our study was excellent with all patients alive and disease free at last follow up. For ovarian SCST, we recommend Complete Surgery (TAH + BSO) particularly if high grade, Stage IC and above or completed childbearing to minimize recurrence. Fertility sparing surgery is appropriate for all patients with Stage I Ovarian GCT and most of the patients with Stage II disease who desire fertility preservation.

Clinicopathologic characteristics of epithelial ovarian tumours in Ile-Ife, Nigeria

Background: Epithelial ovarian tumours (EOT) have complex clinicopathologic characteristics and biological behaviours. There are benign, borderline and malignant ovarian tumours and the commonest ovarian tumours in many regions are of epithelial origin. Many studies have described the histomorphological characteristics of the tumours. Objective: To describe the clinical and histopathological features of epithelial ovarian tumours. Methods: This was a retrospective review of the histopathology reports of all epithelial ovarian tumours specimens submitted to the Department of Morbid Anatomy and Forensic Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife from January 2005 to December 2014. The EOT cases were described in terms of age, clinicopathological characteristics and distribution of histological types. Results: The frequencies of benign, borderline and malignant EOTs were 41.2%, 3.9% and 54.9% respectively and the patients were aged 23 to 94 years (mean 46.5±2.6 years). The majority of cases were often asymptomatic. Conclusion: Abdominal swelling was the most common presenting complaint while serous ovarian tumours were the most preponderant histological types.

Immunoexpression of Epidermal Growth Factor Receptor (EGFR) in Malignant Surface Epithelial Tumours of Ovary

Ovarian cancer is the deadliest gynaecological cancer and approximately 70% are diagnosed in an advanced stage with 5 years survival rate of only 35%. The aim of this study was to find out the distribution of epidermal growth factor receptor (EGFR) immunoexpression in different histological types and grades of malignant surface epithelial tumours of ovary. A total 54 cases of malignant surface epithelial tumours of ovary from North Okkalapa General and Teaching Hospital and Thingangyun Sanpya General Hospital from August 2015 to September 2016 were included. This study included 30 cases (56%) of serous tumour, 18 cases (33%) mucinous tumour, 5 cases (9%) clear cell tumour and one case (2%) of malignant Brenner tumour. Of the 54 cases, 11 cases (20%) were well differentiated, 33 cases (61%) moderately differentiated and 10 cases (19%) poorly differentiated tumours. Different histological types and grades of malignant surface epithelial ovarian tumours were determined for EGFR immunoexpression by peroxidase antiperoxidase method. Out of 54 cases, 31 cases (57.4%) were found to be positive for EGFR immunoexpression and 23 cases (42.6%) showed negative immunoexpression. Among 31 positive cases of EGFR, 54.8% were serous, 32.3% mucinous, 9.7% clear cell and 3.2% were malignant Brenner tumour. The highest EGFR immunoexpression was found in malignant serous, tumour (54.8%). Regarding the histological grades of the 31 positive cases, EGFR immunoexpression was found 9.7% in well differentiated, 64.5% moderately differentiated and 25.8% in poorly differentiated tumours. Increased EGFR immunoexpression was observed predominantly in higher histological grades of ovarian cancers. Since, high EGFR levels have a negative prognostic role in ovarian cancers, further studies with long-term follow-ups are required to determine the prognosis and management of patients with malignant surface epithelial ovarian tumours.