The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNgamma-induced cell death in human ovarian carcinoma cells.

H-rev107-1 is a growth inhibitory RAS target gene capable of suppressing anchorage independent growth in vitro and in vivo. Using a tumour tissue array with 241 matched tumour and normal tissue cDNA pools, we found down-regulation of H-REV107-1 in 7 out of 14 ovary-derived cDNAs. RT-PCR analysis and immunohistochemical investigation confirmed expression of H-REV107-1 in normal ovarian epithelial cells but down-regulation in high grade ovarian carcinomas. H-REV107-1 is also strongly expressed in immortalized rat and human ovarian epithelial cells in vitro, but suppressed in transformed cells by two different mechanisms. KRAS-transformed rat ovarian cells and PA1 teratocarcinoma cells, reversibly repress H-REV107-1 via MAP/ERK signaling. In contrast, treatment of A27/80 and OVCAR-3 epithelial ovarian cancer cells with IFNgamma stimulated H-REV107-1 expression. In NIH3T3 cells harbouring an estrogen-inducible IRF-1, H-rev107-1 is directly induced after activation of IRF-1, indicating that H-rev107-1 is a target of IRF-1. Stimulation of H-REV107-1 expression was also observed in ovarian epithelial cells suggesting that IRF-1 is involved in H-REV107-1 regulation in human ovarian epithelium. In the IFNgamma-sensitive cell line A27/80, H-REV107-1 suppresses colony formation. A27/80 and OVCAR-3 cells overexpressing H-REV107-1 protein underwent apoptosis. These results demonstrate down-regulation of the class II tumour suppressor H-REV107-1 in human ovarian carcinomas and suggest an involvement of H-REV107-1 in interferon-dependent cell death.

Loss of Gelsolin expression in human ovarian carcinomas.

The ubiquitously expressed actin-binding protein, gelsolin, is known to play a role in the modulation of the actin network and in the regulation of cell growth and cell motility. In the present study, we analysed the expression of gelsolin in 241 matched cDNA pairs from human normal and tumour tissues using a Cancer Profiling Array. We found a decreased expression of gelsolin in cancer tissue from female reproductive organs, including the ovary. On a protein level, we examined the expression of gelsolin in human ovarian cancer cell lines and in a set of 110 cases of human benign and malignant ovarian tumours. Low levels of gelsolin protein were observed in four of six ovarian carcinoma cell lines, in contrast to its expression in normal ovarian surface epithelial cells. In addition, we found a reduced expression of gelsolin in borderline tumours and ovarian carcinomas compared with the epithelium of normal ovaries and benign adenomas. Decreased gelsolin expression was associated with poorly differentiated carcinomas (p=0.014). No significant association between gelsolin expression and other clinicopathological markers or patient survival could be established. In addition, we investigated the growth regulatory function of gelsolin in human ovarian cancer cell lines using cDNA transfections. Re-expression of gelsolin in OAW42 and ES-2 cells resulted in a suppression of tumour cell survival in vitro. To explore the mechanism responsible for the downregulation of gelsolin expression in ovarian carcinoma cells, we treated cells with inhibitors of DNA methylation and histone deacetylation. We observed an upregulation of gelsolin in ovarian cancer cells after treatment with both types of inhibitor. Our results suggest that gelsolin might be involved in the growth regulation of human ovarian cancer.

Formalin-fixed blood clots--additional histological findings on computed tomography-guided fine-needle aspiration biopsies in comparison with core biopsies.

OBJECTIVE: We investigated the diagnostic yield of histological examined formalin-fixed blood clots (FFBCs) in comparison with the established procedures of fine-needle aspiration biopsy (FNAB) and core biopsy (CB) obtained by percutaneous puncture under computed tomography (CT) guidance. METHODS: A total of 76 CT-guided punctures with removal of tissue by means of all 3 different techniques (FFBC, FNAB, and CB) were performed. Specimens were obtained from the lung (n=18), mediastinum (n=10), upper abdominal organs (n=32), pelvis (n=4), retroperitoneum (n=4), bones (n=7), and neck (n=1). All results were correlated with the clinical course of the patients (minimum, 6 months; mean period, 10 months). The results of each technique were compared. Results of a combined use of FFBC and FNAB were analyzed. RESULTS: The overall sensitivity (regardless of biopsy site) was 79% for FFBC, 83% for FNAB, and 95% for CB. In chest biopsies, FFBC reached a sensitivity of 92%, FNAB of 86%, and CB of 96%. In liver biopsies, the sensitivities were 47%, 70%, and 88% for FFBC, FNAB, and CB and, for the remaining biopsy sites, 90%, 90%, and 100%, respectively. The combination of FFBC and FNAB showed higher sensitivities than FFBC and FNAB alone. Overall sensitivity for the combination was 88%, with 92%, 72%, and 100% for thorax, liver, and other locations. A definitive diagnosis was made by FFBC in 87% of cases, by FNAB in 74%, and by CB in 88%. The combination of FFBC and FNAB showed a definite diagnosis in 90% of the cases. A tentative diagnosis has been established in 12%, 7%, 5%, and 4%, respectively. In 4 cases (5%), all 3 techniques failed to yield reliable diagnoses. CONCLUSIONS: The examination of FFBCs is a useful supplement to the established technique of CT biopsy. In combination with FNAB, FFBC has a comparable sensitivity as CB in chest punctures and other extrahepatic lesions.

Systematic identification and molecular characterization of genes differentially expressed in breast and ovarian cancer.

The identification of novel disease-associated genes in gynaecological tumours has important implications for understanding the process of tumourigenesis and the development of novel treatment regimens. cDNA libraries from disease tissues may represent a valuable source to identify such genes. Recently, a bio-informatic procedure based on an 'electronic Northern' approach was established to screen expressed sequence tag (EST) libraries for genes differentially expressed in tumour and normal tissues, and identified 450 candidate genes differentially expressed in breast and ovarian cancer. In this report, the validation of an initial set of 40 candidate genes, which were selected due to their localization in chromosomal regions frequently altered in gynaecological tumours, is described. Differential expression of 29 of these genes, including three uncharacterized novel genes, was confirmed by applying cancer profiling arrays with 106 matched pairs of tumour/normal cDNAs and quantitative reverse transcription-polymerase chain reaction (RT-PCR) on 60 clinical specimens. The majority of these differentially expressed genes have not been described previously in the context of breast and ovarian cancer, and may constitute novel diagnostic markers for these tumour entities.