Biochemical and morphological differences between CA125 isolated from healthy women and patients with epithelial ovarian cancer from Tunisian population.

Analysis of the structure of CA125 is essential for determining the physiological role of this significant tumor antigen. The objectives of this study were: (1) to identify the characteristics of the CA125 isolated from healthy and patient women with epithelial ovarian cancer; and (2) to determine the ferning structure of this antigen. The cancer-derived CA125 antigen (cCA125) purified by gel filtration and affinity chromatography (Concanavalin A) was run on SDS-PAGE and examined using light microscopy and compared with healthy-derived CA125 antigen (hCA125). Both purified antigen cCA125 and hCA125 showed a high molecular mass (> 2,000 kDa) with high mannose glycans. The ferning patterns related to cCA125 and hCA125 revealed distinct differences in the patterns of arborescence. The ferning morphology of cCA125 antigen was denser than that of hCA125 antigen making an obvious difference between cCA125 and hCA125, with respect to length, branching and distribution of crystals. The current study provides the first evidence for a potential functional link between CA125 and its structure which, in the light of a comparison between cCA125 and hCA125, might proof to be of significant biomedical importance in the future.

Correlation between Heterogeneous Expression of Sialyltransferases and MUC16 in Ovarian Tumor Tissues.

BACKGROUND: A number of glycoproteins such as CA125 are abnormally glycosylated in ovarian cancers. Most aberrant glycosylations are a result of altered sialyltransferase (ST) expression. The aim of this study was to evaluate the expression of 6 STs and MUC16, and their correlations in benign and malignant ovarian tissues. MATERIAL AND METHODS: mRNA expression of 6 STs and MUC16 was assessed in 16 human ovarian tumors (7 benign, 9 malignant) by real-time quantitative polymerase chain reaction (RTQ-PCR). RESULTS: mRNA of ST6GAL I and ST3GAL I was not significantly upregulated in ovarian cancer tissues, while ST6GAL II and ST3GAL IV were not significantly increased in benign tumors. There was no change between ST3GAL III and ST3GAL VI expression and tumor subtypes. MUC16 was significantly increased in carcinoma tissue. Significant correlation was found between ST3GAL III and ST3GAL IV. MUC16 correlated with ST3GAL VI and ST6GAL I. ST6GAL I correlated well with ST3GAL VI. ST6GAL II correlated significantly with ST3GAL III and ST3GAL IV. CONCLUSIONS: The given STs and MUC16 can be expressed at a heterogeneous level as a consequence of oncogenic transformation of the ovary. A strong correlation between MUC16 and STs may impact specifically on the glycosylation of MUC16.

Polymorphisms in the MUC16 gene: potential implication in epithelial ovarian cancer.

MUC16 plays an important role in epithelial ovarian cancer. In this paper, we studied the association between two tags SNPs of MUC16 and the risk of epithelial ovarian cancer. We aimed also to test the association between these tags SNPs and elevated level of the protein CA125. We analyzed a collection of 117 cases. Forty-one samples of patients with epithelial ovarian cancer and 76 samples from Tunisian volunteers were genotyped for two synonymous coding tags SNPs of the MUC16 gene (rs1596797, A/C and rs2547065, C/G) using polymerase chain reaction and sequencing. For the rs1596797 SNP, there was no significant difference in genotype distribution, a rare variation observed in only one patient. For the polymorphism rs2547065, mean CA125 levels were 24 and 78 UI/ml in patients with GG and GC genotypes versus 230 UI/ml in patients with CC genotype (P = 0.36). Compared to the C/C genotype, the 'G' allele (C/G+G/G genotypes) did not significantly modified the risk of developing epithelial ovarian cancer (OR = 0.43; 95% CI). As for the polymorphism rs1596797, compared to the C/C genotype, the 'A' allele (C/A+A/A genotypes) did not significantly modified the risk of developing epithelial ovarian cancer (OR = 881.7; 95% CI). MUC16 gene polymorphisms selected in this study are neither involved in genetic predisposition to epithelial ovarian cancer nor associated with CA125 level.

Conflicting views on the molecular structure of the cancer antigen CA125/MUC16.

CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker.

Factors predictive of elevated serum CA125 levels in patients with epithelial ovarian cancer.

Our objective was to identify factors that correlate with high CA125 (cancer antigen 125) concentrations in Tunisian women with epithelial ovarian cancer and to introduce recommendations for reporting and interpreting individual CA125 assay results. We analyzed repeated serum CA125 levels, by the immunoenzymatic assay using an AxSym CA125 kit, in 90 patients who were treated for ovarian cancer from 1994 to 2006 in CHU Farhat Hached Sousse Tunisia. Using a logistic model, we found that carcinosis is significantly predictive of high levels of serum CA125 (p = 0.005). A woman's age (> or = 45 years, p = 0.016) and menopausal status (postmenopausal patient, p = 0.034) are also predictive of increased CA125 concentration. Patients with serous histological subtype have higher CA125 values (p = 0.001). Presence of ascites is associated with high serum CA125 values and thus could be considered as a predictor of high serum CA125 concentration (p = 0.023). The International Federation of Gynecology and Obstetrics stage and primary tumor size are not significant predictors of CA125 concentrations (p > 0.05). We conclude that clinically significant parameters should lead to the best interpretation of rising CA125 levels and consequently to more appropriate management of epithelial ovarian cancer patients.