OBJECTIVETo identify potential miRNA involved in epithelial ovarian cancer (EOC) invasion and metastasis.

METHODSmiRNA microarray was applied to compare the miRNA expression profile between SKOV-3ip and SKOV-3 cells. Bioinformatics programs (TargetScan, MicroCosm, PicTar and GO) were used to analyze the miRNA and their potential target genes. Real-time RT-PCR was used to confirm the results of microarray and for expanding detection in another paired EOC cell lines (HO-8910 and HO-8910PM).

RESULTSTotally, expressions of 42 miRNA were found significantly different between SKOV-3ip and SKOV-3 cells. Among them, 10 miRNA were down-regulated, including let-7a, let-7f, miR-22 and miR-886-5p; while 32 were up-regulated, for example, let-7e and miR-519e. Bioinformatic analysis indicated that let-7a, let-7e, let-7f, miR-22 and miR-886-5p may be involved in cancer invasion and metastasis. Meanwhile, real-time RT-PCR confirmation and statistic analysis showed that let-7f and miR-22 expressions were significantly different between ovarian cancer cell lines with various invasive and metastatic capacity (P < 0.05).

CONCLUSIONThe expression of let-7f and miR-22 is low in ovarian cancer cells with high invasive and metastatic capacity. It suggests that they are potential tumor suppressor genes. Further research on their role and mechanism is needed.

Cell Line, Tumor ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; Gene Expression Profiling ; Humans ; MicroRNAs ; genetics ; metabolism ; Microarray Analysis ; methods ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Ovarian Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVETo detect the expression of human similar expression to FGF gene(hSef) and fibroblast growth factor-2(FGF-2) and their correlation with epithelial ovarian tumor.

METHODSImmunohistochemical SP staining was used to detect the expression of hSef and FGF-2 proteins in 31 cases of epithelial ovarian carcinoma (EOC), 18 cases of benign epithelial tumor (BET), 10 cases of normal ovarian (NO) tissues collected from July 2007 to May 2008. The expression of hSef mRNA in 24 cases of EOC, BET and NO collected from July 2008 to May 2009 were analyzed by RT-PCR.

RESULTSThe results of immunohistochemical study showed that the expression of hSef in the EOC tissues were significantly lower than that in the NO and BET (P < 0.001). However, the expression of FGF-2 was higher (P = 0.002). The expression of hSef had a negative correlation with FGF-2 (r(s) = -0.324, P = 0.012). The RT-PCR results showed that there was a gradually declined trend of expression of hSef in NO, BET to EOC (P < 0.001), but the expression of FGF-2 in NO, BET to EOC was gradually increased (P < 0.001), with a significant negative correlation (NO: r(s) = -0.910, P < 0.001; BET: r(s) = -0.859, P < 0.001; EOC: r(s) = -0.888, P < 0.001).

CONCLUSIONSThe expression of hSef is decreased in epithelial ovarian carcinoma tissue, but the expression of FGF-2 is increased. It is likely that low hSef expression is related to the the carcinogenesis and development of epithelial ovarian carcinoma by suppressing the promoting effects of FGF-2 to cell proliferation.

Adult ; Aged ; Cystadenocarcinoma, Mucinous ; genetics ; metabolism ; pathology ; surgery ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; surgery ; Cystadenoma, Mucinous ; genetics ; metabolism ; pathology ; surgery ; Cystadenoma, Serous ; genetics ; metabolism ; pathology ; surgery ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Ovary ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Interleukin ; genetics ; metabolism

Animals ; Biomarkers, Tumor ; genetics ; metabolism ; Cell Nucleus Division ; Cystadenocarcinoma, Serous ; classification ; genetics ; metabolism ; pathology ; Female ; Humans ; Mutation ; Neoplasm Grading ; Ovarian Neoplasms ; classification ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVETo investigate the expression of EVEC in ovarian carcinoma and explore its biological significance.

METHODSThe expression of EVEC in 22 specimens of normal ovarian tissues and 63 specimens of ovarian cancers was detected by RT-PCR and Western blotting analysis, respectively.

RESULTSRT-PCR showed that the expression level of EVEC in stage I-II ovarian cancer (0.199 ± 0.014) was significantly higher than that in stage III-IV ovarian cancer (0.155 ± 0.015, P < 0.05), and significantly lower than that in normal ovarian tissues (0.415 ± 0.055, P < 0.05). There was no significant difference between the expression levels of EVEC in primary sites and that in corresponding metastatic sites of ovarian cancer (P > 0.05). Furthermore, the results of Western blot also showed that the protein expression level of EVEC in stage I-II ovarian cancer was also significantly lower than that in normal ovarian tissues (0.179 ± 0.026 vs. 0.543 ± 0.032, P < 0.05), and higher than that in stage III-IV ovarian cancer (0.179 ± 0.026 vs. 0.115 ± 0.023, P < 0.05). The EVEC expression level in the epiploic metastasis of stage I-II ovarian cancer was significantly higher than that of stage III-IV ovarian cancer (0.201 ± 0.028 vs. 0.101 ± 0.037, P < 0.05). The expression of EVEC in ovarian carcinoma had no correlation with age, pathologic classification and histological grade (P > 0.05).

CONCLUSIONSEVEC is closely related with carcinoma metastasis. The expression of EVEC in ovarian cancer and its metastatic sites was remarkably decreased. EVEC may play a negative role in the development and metastasis of ovarian cancer and may be a valuable marker in estimation of the prognosis for patients.

Adult ; Carcinoma, Endometrioid ; genetics ; metabolism ; pathology ; secondary ; Cystadenocarcinoma, Mucinous ; genetics ; metabolism ; pathology ; secondary ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; secondary ; Extracellular Matrix Proteins ; genetics ; metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Omentum ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Ovary ; metabolism ; Peritoneal Neoplasms ; genetics ; metabolism ; secondary ; RNA, Messenger ; metabolism

OBJECTIVETo investigate the expression of mesothelin (MESO) mRNA and protein and its significance in ovarian carcinomas.

METHODSSemi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect the expression level of MESO mRNA and protein, respectively, in 124 samples of ovarian tumor and normal tissues, including 84 epithelial ovarian carcinomas, 12 borderline ovarian tumors, 16 benign ovarian tumors and 12 normal ovarian tissues.

RESULTSThe expression of MESO mRNA and protein in epithelial ovarian carcinomas (1.4005 +/- 0.4646, 2.7857 +/- 2.2712) and borderline ovarian tumors (1.0650 +/- 0.3100, 2.9167 +/- 2.391) were significantly higher than that in benign ovarian tumors (0.6463 +/- 0.2419, 1.2500 +/- 1.6125) and normal ovarian tissues (0.6439 +/- 0.2729, 0.9167 +/- 1.2401) (P < 0.05), and also significantly higher in serous cystadenocarcinoma (1.5255 +/- 0.4151, 3.3036 +/- 2.6141) and endometrioid carcinoma (1.5250 +/- 0.5419, 3.0000 +/- 2.3094) than that in mucinous cystadenocarcinoma (1.0675 +/- 0.3149, 1.0556 +/- 1.9242) (P < 0.05). The expression of MESO mRNA and protein in stages II and IV carcinomas (1.5100 +/- 0.4142, 3.6087 +/- 3.3959) was significantly higher than that in stages I and II carcinomas (1.1190 +/- 0.4909, 1.7895 +/- 2.6320; P < 0.05), and also significantly higher in grade 3 carcinomas than that in grade 1 and 2 ones (P < 0.05), but was not correlate with age or serum CA125 of the patients (P > 0.05).

CONCLUSIONThe results of this study demonstrated that the expression of MESO mRNA and protein is increased in ovarian carcinomas and borderline ovarian tumors, and MESO may play a role in the adhesion and dissemination of ovarian carcinomas.

Carcinoma, Endometrioid ; genetics ; metabolism ; pathology ; Case-Control Studies ; Cystadenocarcinoma, Mucinous ; genetics ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; GPI-Linked Proteins ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Membrane Glycoproteins ; metabolism ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Ovary ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the significance and mechanisms of overexpression of p21-activated kinase 1 gene (PAK1) in epithelial ovarian neoplasms.

METHODSImmunohistochemistry, fluorescence in situ hybridization and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling methods were used to examine the protein expression and amplification of PAK1 and cell apoptosis in 30 benign ovarian adenomas, 20 borderline tumors and 80 ovarian carcinomas by tissue microarray.

RESULTSIn immunohistochemistry study, overexpression of PAK1 protein was observed in 7 (25.9%) informative benign ovarian adenomas, 7 (36.8%) borderline tumors and 53 (68.8%) ovarian carcinomas. A significant inverse correlation of PAK1 overexpression and cell apoptosis was observed in these epithelial ovarian neoplasm cohorts (P = 0.002). In addition, 27/31 (87.1%) poorly differentiated (G3) carcinomas showed overexpression of PAK1, the frequency was significantly higher than that in tumors of G1 - G2 (26/46, 56.5% , P =0.01). In fluorescence in situ hybridization study, only 2 (4.7%) informative ovarian carcinomas showed amplification of PAK1 gene. None of the borderline and benign ovarian tumors showed PAK1 amplification.

CONCLUSIONOverexpression of PAK1 protein may be involved in the tumorigenesis of epithelial ovarian neoplasms and it is associated closely with the malignant histological phenotype of ovarian carcinomas. Mechanism other than gene amplification of PAK1 may play a more important role in the regulation of protein expression of PAK1 in ovarian tumors.

Adenoma ; genetics ; metabolism ; pathology ; Apoptosis ; Cystadenocarcinoma, Mucinous ; genetics ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; In Situ Nick-End Labeling ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; p21-Activated Kinases ; genetics ; metabolism

OBJECTIVEto investigate the expression of folate receptor(FR)α in ovarian epithelial tumors and its clinopathological significance.

METHODStissue microarrays (TMAs) were constructed from 86 epithelial ovarian cancers and 29 borderline ovarian tumors, followed by the FRα expression evaluation by immunohistochemistry. FRα mRNA expression was investigated by quantitative real-time PCR using fresh-frozen tissues from 40 cases of ovarian carcinoma and 14 cases of borderline tumor. FRα expression levels in ovarian tumors were also analyzed in correlation with tumor morphology, pathogenesis and FIGO stage.

RESULTSFRα expression was detected in 40 of 86 (46.5%) of ovarian cancers, with the highest rate of expression observed in serous carcinomas (62.7%, 32/51) compared with that of the other cancer types (P = 0.000). Depending on pathogenesis type, FRα expressions in type II ovarian carcinomas were significantly higher than those in type I ovarian carcinomas (P = 0.001). Ovarian carcinomas had a tendency to express higher FRα than the borderline tumors (46.5% vs 27.6%), although statistically not significant (P = 0.074). FRα expressions in ovarian carcinomas showed no correlation with the FIGO stage (P = 0.498). However, real-time PCR showed that FRα mRNA levels were significantly higher in ovarian carcinomas compared with that of the borderline tumors (P = 0.000) and also higher in serous ovarian borderline tumors compared with mucinous type (P = 0.007).

CONCLUSIONhigher level of FRα expression occurs frequently in ovarian epithelial tumors, especially in carcinomas and ovarian serous tumors.

Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adult ; Aged ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; Female ; Folate Receptor 1 ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Young Adult

Age of Onset ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Receptors, Progesterone ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the expression of two major alternative transcripts of RASSF1 gene (RASSF1A and RASSF1C) in human primary ovarian cancers and their biological implication as a new tumor suppressor gene.

METHODSReverse transcription-polymerase chain reaction (RT-PCR) and laser capture microdissection (LCM) were used to determine mRNA expression of the two major alternative transcripts of RASSF1 gene (RASSF1A and RASSF1C) in 3 ovarian cancer cell lines and 80 cases of primary ovarian cancers.

RESULTSRASSF1A mRNA was undetectable in SK-OV-3 cell line. Expression of RASSF1A and RASSF1C in 80 primary ovarian cancers were 40.0% (32/80) and 91.3% (73/80) respectively. RASSF1A mRNA expression was detectable more frequently in stage I and II (71.4%, 10/14; 75.0%, 9/12) than in stage III and IV ovarian cancers (26.7%, 12/45; 14.1%, 1/9) (P < 0.05). The expression level was also higher in well and moderately differentiated tumor groups (58.6%, 17/29; 50.0%, 10/20) than in poorly differentiated tumor group (16.1%, 5/31) (P < 0.05).

CONCLUSIONThere is a preferential loss of RASSF1A expression in human ovarian cancers and its expression is correlated with the tumor stage and the degree of histological differentiation which, as a tumor suppressor gene, might play an important role in the tumorigenesis of human primary ovarian cancer.

Carcinoma, Endometrioid ; metabolism ; pathology ; Cell Line, Tumor ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVETo investigate the expression of dipeptidyl peptidase IV (DPPIV) in patients with epithelial ovarian carcinoma (EOC) and its clinical significance.

METHODSImmunohistochemistry (IHC) was used to detect the expression of DPPIV protein in 378 formalin-fixed paraffin-embedded EOC tissue samples. The expression of DPPIV mRNA in 86 EOC tissue samples were examined by in situ hybridization (ISH) using specific FITC-labelled RNA probes. Forty-two samples of normal ovarian tissues were used as control. Statistical analyses were carried out by Chi-square test, Spearman rank correlation and Kaplan-Meier method.

RESULTSAmong the 378 epithelial ovarian carcinomas, 351 (92.9%) showed a positive expression of DPPIV protein, while only 25/42 (59.5%) of normal ovaries had a positive expression by semi-quantitative IHC analysis. The expression level of DPPIV protein was significantly lower in the normal ovaries than that in ovarian carcinomas (chi(2) = 18.4, P = 0.001). There was no significant correlation between the expression of DPPIV protein and age, FIGO stage and histological grade (P > 0.05). However, the expression of DPPIV protein was significantly associated with histological type (chi(2) = 28.5, P = 0.005). The patients with high level expression of DPPIV protein likely had a poor prognosis in terms of overall survival (P = 0.02). Of the 86 patients, 84 (97.7%)showed positive expression of DPPIV mRNA, also higher than that in normal ovarian tissues (P < 0.05). A statistically significant correlation between DPPIV mRNA and protein expression was observed (r(s) = 0.66, P = 0.001).

CONCLUSIONDPPIV may be involved in the carcinogenesis of ovarian cancer, and may become a potential prognostic marker for epithelial ovarian carcinoma.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Dipeptidyl Peptidase 4 ; biosynthesis ; genetics ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; RNA, Messenger ; metabolism ; Survival Rate