Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer / 대한산부인과학회지

OBJECTIVE: The purposes of this study were to examine the expression of matriptase, and its inhibitor, HAI-1, in epithelial ovarian cancer and to assign clinicopathological correlations and to discuss the matriptase/inhibitor (HAI-1) system in the context of ovarian cancer and to examine the possibility that this system might be a useful therapeutic target in this disease. METHODS: A retrospective study was performed in 51 patients with primary epithelial ovarian cancer staged over Ic who have been diagnosed and treated at Kyung Hee university medical center from Jan. 1991 to Mar. 2003. They were managed with cytoreductive surgery and chemotherapy. This study was performed in paraffin embedded blocks of primary epithelial ovarian cancer of 51 patients by means of immunohistochemistry. In addition, to validate protein expression data at the gene level, matriptase/HAI-1 mRNA expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) on frozen specimens from 10 ovarian cancers. Statistical analyses of immunohistochemistry (IHC) expression data with clinicopathological parameters and survival were then performed. RESULTS: Of 51 ovarian tumors tested, 25 (49%) and 37 (72.5%) were positive staining for matriptase and HAI-1 by IHC, respectively. Of 18 stage I/II tumors, 11 (61.1%) stained positive for matriptase, and 15 (83.3%) stained positive for HAI-1; Of 18 stage I/II tumors, 10 (55.6%) tumors showed coexpression. Of 33 stage III/IV tumors, 14 (42.4%) stained positive for matriptase and 22 (66.7%) stained positive for HAI-1; Of 33 stage III/IV tumors, 11 (33.3%) tumors showed coexpression. CONCLUSION: No relationship was found between the expression of either matriptase or HAI-1 with clinicopathological parameters and survival. However, stage I/II ovarian tumors are more likely to express matriptase and HAI-1 than are the more advanced disease stage III/IV tumors. Correspondingly, the low frequency of matriptase and HAI-1 coexpression is more likely to be associated with stage III/IV tumors than stage I/II tumors. Such an imbalance in the matriptase: HAI-1 ratio could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype in the advanced tumors.

Abnormal Fragile Histidine Triad (FHIT) Expression in Cervical Carcinomas / 대한산부인과학회잡지

OBJECTIVE: The fragile histidine triad (FHIT) gene is located at chromosome 3p14.2 and encompasses the common fragile site, FRA3B, which may contribute to chromosome breakage and rearrangement of cancer cells. In this study, we examined whether transcriptional alterations of FHIT gene play a role in the development of human cervical carcinomas and the possibility that hypermethylation of CpG islands serves for FHIT inactivation. We then analyzed FHIT expression status with clinical parameters to determine whether it has any prognostic significance. METHODS: The study group included 50 squamous carcinomas, 4 adenocarcinomas, 4 adenosquamous carcinomas, 7 noncancerous tissue and the clinical stage is composed of 4 Ia, 37 Ib and 17 II. Tissue specimens were snap-frozen in liquid N2 and stored at -70degrees C until used. To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR. RESULTS: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. CONCLUSION: In this study, gene mutation is not a main mechanism for FHIT inactivation, but the aberrant promoter hypermethylation may be correlated with decreased expression of the FHIT gene. The significance of decreased expression of FHIT does not appear to be an independent prognostic factor in cervical cancers, although a still larger sample of patients will be required to asses this issue definitively.

Correlation of Telomerase Activity, hTERT mRNA Expression and HPV E6 Detection in Cervical Cancer Tissue / 대한산부인과학회잡지

OBJECTIVE: Telomerase is a ribonucleoprotein enzyme which stabilizes chromosomal structure, thereby inducing cellular immortality. We investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in cervical carcinomas. METHODS: From December 1995 to December 1999, at the department of obstetrics and Gynecology of Kyung-Hee University Hospital, 32 cervical carcinomas and 5 corresponding nontumor cervical tissues were obtained and the samples were immediately frozen and stored at -70 degree C. Telomerase activity was measured by using telomerase PCR ELISA, a modified version of the TRAP. Analysis of the expression of hTERT mRNA was performed by quantitative RT-PCR and the analysis of the HPV E6 gene was performed by DNA-PCR. RESULT: All of the carcinomas examined exhibited strongly positive for telomerase activity (OD>0.24), whereas telomerase activity was week or not found in the 5 corresponding nontumor cervical tissues. Quantitative RT-PCR analysis demonstrated significantly increased hTERT mRNA expression levels (>0.024) in most carcinomas comparing to control groups. There was no obvious relationship between telomerase activity levels and the clinical parameters examined including age, clinical stage, pathology, differentiation, tumour size, LN involvement and invasion depth except lymphovascular space invasion (p=0.03). In the correlation between the levels of hTERT mRNA expression and telomerase activity, correlation index which was 0.916, shows high correlation (p=0.01). According to the analysis of HPV E6 gene, 29 of 32 (90.6%) carcinomas showed HPV E6 positivity. CONCLUSION: There is a strong association between telomerase activity and hTERT mRNA expression, and up-regulation of hTERT probably plays a role in the progression of cervical carcinomas. Telomerase is at least partially activated by viral oncogenes of high-risk types. There is no obvious relationship between telomerase activity levels and the clinical parameters except LSVI (p=0.03). These findings provides that telomerase may play an important role in the early stage of carcinogenesis.