Expression, Intracellular Localization, and Prognostic Value of Plasminogen Activator Inhibitor 1 and PAI-1 RNA-Binding Protein 1 in Primary and Recurrent Ovarian Cancer: A Study of the Tumor Bank Ovarian Cancer Network.

BACKGROUND: The plasminogen activator system plays a key role in ovarian cancer (OC) tumor progression. The plasminogen activator inhibitor type 1 (PAI-1) and the recently identified PAI-1 RNA binding protein 1 (PAI-RBP1) are primary regulators of plasminogen activation and thus are putative biomarkers for OC progression. METHODS: One hundred fifty six OC patients were analyzed to identify the presence of PAI-1 and PAI-RBP1 and subsequently correlated to clinicopathological parameters. Primary cells obtained from OC patient samples were applied in fluorescence microscopy analysis for examination of PAI-1 and PAI-RBP1 distribution. RESULTS: PAI-1 and PAI-RBP1 have been found to be predictive markers for OC patients' outcome. PAI-1 levels significantly correlated with volume of ascites, FIGO staging, and lymph node status. PAI-RBP1 expression significantly correlated with age at first diagnosis, histological tumor type, presence of distant metastasis (pM), and recurrence. PAI-1 showed a trend toward association and PAI-RBP1 was significantly associated with progression-free survival. Notably, PAI-1 protein in recurrent OC tissues was exclusively localized in the nucleus. CONCLUSION: This study has shown that a combination of PAI-1 and PAI-RBP1 may represent novel prognostic factor for OC. Prospective trials are needed.

The -463G/A polymorphism in myeloperoxidase gene and cervical cancer.

BACKGROUND: Cervical cancer is the leading cause of cancer-related death in women in developing countries. The -463 type G polymorphism of the MPO gene has been correlated with higher MPO expression and increased risk of various types of cancers. Our study was performed in order to evaluate the association between the -463G polymorphism and the prevalence of cervical cancer. MATERIALS AND METHODS: In our prospective study, 149 patients with cervical cancer and 126 patients without any malignancies were enrolled. RESULTS: No significant difference was found between genotype distributions in the cervical cancer patients and the control group. There was also no significant association of the genotype distributions with clinical prognostic factors. However, significantly lower A allele frequency of the -463 polymorphism of the MPO gene was found in our study group in comparison with that of the average Caucasian population. CONCLUSION: The -463 polymorphism of the MPO gene was not associated with susceptibility to cervical cancer.

Expression of IL-10 in patients with ovarian carcinoma.

BACKGROUND: Cytokines are involved in the pathogenesis of different gynecological malignancies. Additionally, they stimulate the spread of cancer cells. Interleukin 10 (IL-10) was described as a pro-inflammatory factor and seems to be implicated in the immune deficiency of patients with cancer. The aim of this study was to determine whether the level of IL-10 in the serum and ascites was associated with the prognosis of advanced ovarian cancer (OC). MATERIALS AND METHODS: In a prospective study from 2001 to 2003, the concentration of IL-10 in the serum and ascites of 117 consecutive patients with advanced OC and 30 women with benign disease who underwent surgery as a control group (CG), was analyzed by the enzyme-linked immunosorbent assay. For statistical analyses, the Chi-square test by Pearson, Fisher's exact test and the Mann-Whitney test were employed. RESULTS: The concentrations of IL-10 were a median of 9.87 pg/ml (range 7.8 to 500 pg/ml) in the serum and a median of 43.70 pg/ml (range 7.8 to 389.4 pg/ml) in the ascites of the OC patients. The IL-10 level in the sera of the CG was a median of 7.80 pg/ml (range 7.8 to 62.8 pg/ml) and 18.34 pg/ml (range 7.8 to 88.72 pg/ml) in the peritoneal fluid. A significant association was observed between the IL-10 serum levels (p = 0.003) and levels in the peritoneal fluid (p = 0.03) in both OC and the CG. IL-10 was significantly more expressed in the ascites of patients with OC than in their sera (p = 0.003). The concentration of IL-10 correlated significantly with proven conventional prognostic factors such as recurrence status (p = 0.005), volume of (ascites, p < 0.001, serum, p = 0.03), histological grading (p = 0.053) and histological type (ascites p = 0.005/ serum p = 0.09). There was no significant correlation between the levels of lL-10 in the ascites and/or serum and FIGO stage, residual tumor mass or age. The cut-off value of 8.0 pg/ml for IL-10 serum levels had a positive predictive value of 84% (95% CI: 76-91) and a negative predictive value of 29% (95% CI: 16-41), with a specificity and sensibility of 47% (95% CI: 29-65) and 70% (95% CI: 62-78), respectively. CONCLUSION: Due to the fact that the levels of IL-10 were significantly higher in the ascites and serum of OC patients than in those of the CG, IL-10 may play an important immunosuppressive role in the pathogenesis of OC. The association between high IL-10 levels in ascites and serum and the histological type of the tumor, as well as between the levels in the peritoneal cavity and grading, suggest that IL-10 could be a prognostic factor in OC.

Interleukin 1 receptor antagonist (IL-1RA) polymorphism in women with cervical cancer.

BACKGROUND: Several studies suggest that immunological components play a key role in the development of cervical cancer. Polymorphism in the IL-1 RA gene was associated with various malignant diseases. Data is lacking for cervical cancer. MATERIALS AND METHODS: In a prospective study we analysed the polymorphism of IL-1RA in 113 women with cervical cancer and 107 with benign diseases. Genomic DNA fragments were amplified by PCR. RESULTS: The distribution of genotype frequencies was different between the study and control group with respect to allele 2 heterozygotes (24.8% vs. 13.1%; p = 0.04) but not in the frequencies of allele 1/3 and homozygous allele 2. There were no differences between IL-1 RA 1/2 polymorphism and all other alleles in tumour stage, grading, recurrence status and age. CONCLUSION: This data supports the role for allele 2 of the gene encoding for IL1-RA as a genetic determinant of cervical cancer.