Objective Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression. Methods 4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting. Results Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p < 0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p < 0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p = 0.004), ascites (p = 0.009), omental metastasis (p = 0.018), suboptimal debulking (p = 0.024), poorly histological differentiation (p = 0.009), high-grade serous carcinoma (p = 0.001), short progression-free-survival (p = 0.018) and poor chemosensitivity to first-line chemotherapy (p = 0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines. Conclusions 4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.

ObjectiveRecently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined.MethodsCancer cells SKOV3.ip1 were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ip1 exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mitochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight (MALDI-TOF/TOF), and finally a selected protein candidate was further investigated by immunohistochemistry (IHC) method in nude mice bearing tumor tissues of these two cells.ResultsA total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis (PAGE) approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ip1 cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 (SOD2), fumarate hydratase (FH), mitochondrial ribosomal protein L38 (MRPL38), and mRNA turnover 4 homolog (MRTO4). An increased staining of SOD2 was observed in SKOV3.ip1 over that of SKOV3 in IHC analysis.ConclusionsOur results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.

OBJECTIVE:To investigate whether the molecular classification of endometrial cancer based on gene expression profiles can predict the biological behavior of the tumors and inform prognosis.METHODS:An array containing 492 genes was used to generate gene expression profiles from 35 tumor samples. A hierarchical cluster algorithm was used to compare gene expression patterns among the tumor samples.RESULTS:A cluster analysis revealed 3 distinct tumor clusters. A comparative analysis of tumor type, grade, FIGO stage, and depth of myometrial invasion revealed significant differences in grade and stage among the clusters, which appear to group tumors with specific clinical behaviors. Moreover, the cluster analysis initially revealed 2 clusters of differentially expressed genes. One contained 38 genes that were upregulated in most samples of the cluster representing the most advanced disease, and the other contained 27 genes that were upregulated in most samples of the cluster representing the least advanced disease.CONCLUSION:Molecular classification of endometrial cancer based on gene expression profiles obtained by designing specialized microarrays indicated a marked correspondence with the histologic features and clinical behavior of endometrial cancer tumors.

OBJECTIVES:The use of gasless laparoscopy with an abdominal wall-lifting device for benign gynecological diseases was compared to conventional laparoscopy with CO(2) pneumoperitoneum.METHODS:From February 2007 to July 2007, 76 women with uterine and/or adnexal benign diseases and candidates for laparoscopic surgery were recruited in this study. Thirty-two women underwent gasless laparoscopic surgery and 44 women underwent pneumoperitoneum laparoscopic surgery.RESULTS:Diverse pathologies, including adnexal cyst, uterine myoma and ectopic pregnancy, were treated successfully with gasless laparoscopic surgery. Compared with the patients in the pneumoperitoneum group, the similar hospital stay (P=0.353) and intraoperative blood loss (P=0.157) were observed. However, the mean operative time in the gasless group was significantly longer than that in the pneumoperitoneum group (P=0.003). No severe intraoperative or postoperative complications were found in either group, except for one case of laparotomic conversion in the pneumoperitoneum group due to dense pelvic adhesions. The total hospital charges were significantly less in the gasless group than in the pneumoperitoneum group (P=0.001). In 38 cases of ovarian cyst resection, the mean operative time in the gasless group remained longer than that in the pneumoperitoneum group (P=0.017). The total hospital charges were also significantly less in the gasless group than in the pneumoperitoneum group (P<0.001).CONCLUSION:Our preliminary results demonstrated that the laparoscopic procedure using the gasless technique was a safe, effective method to treat benign gynecological diseases. Moreover, it was easy to master. As a minimally invasive treatment, gasless laparoscopic surgery provides a good choice to patients in the undeveloped regions in China without increasing the patients' and the government's burden significantly.

Background: Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management.Methods: For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers) was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using chi(2) or Fisher's exact test.Results: APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2), endometrial cancer (CASP8, CDH13, hMLH1 and p73), and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1). The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers) were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Aberrant methylation for some genes (BRCA1, DAPK, hMLH1, MGMT, p14, p16, and PTEN) was also associated with clinico-pathological data.Conclusion: Thus, differential methylation profiles occur in the three types of gynecologic cancer. Detection of methylation for critical loci is potentially useful as epigenetic markers in tumor classification. More studies using a much larger sample size are needed to define the potential role of DNA methylation as marker for cancer management.