The Study On Common Fragile Suppressor Genes FHIT And WWOX In Epithelial Ovarial Carcinoma

As one of the most malignant gynecologic tumors,the early symptoms of epithelial ovarian carcinoma are very secret and very easy to metastasize,almost thirty percent patients have cancerous ascites and extensive implantation metastasis when they are diagnosed.The epithelial ovarian carcinoma was characterized by highest mortality rate。Nowadays we consider that tumor is gene disease,the oncogene activation,anti-oncogene inactivation and the change of some modificator genes are benefit to the occurrence and development of tumors.It is becoming an attractive spot to study the anti-oncogene.Fragile histidine triad(FHIT) gene and WWOX gene are first and second anti-oncogenes loading in fragile site,there were some extent expression deletion in lung cancer,breast cancer and so on.Fragile histidine triad(FHIT) was discovered in 1996 as a new anti-oncogene,mapping chromosome 3P^14.2,500Kb,the exon was histidine triad. FHIT protein has AP 3A hydrolytic enzymatic active,which is relate to the function of FHIT protein.WWOX gene maps chromosome16q23.3-24.1, spanning the whole fragile site FRA16D,the two WW structures are relate to interaction of proteins,which is necessary for anti-oncogenes to inhibit tumor growth.The study has showed that the decrease or deletion of FHIT and WWOX genes had significant relationship to tumor progression and prignosis,Our study aimed to approach the expression of FHIT and WWOX in EOC,and further to explore the relationship between expression lever and clinical and pathologic characteristics,then offer the theory basement for treatment,follow-up and prognosis judgement.Objective:To investigate the expressions of FHITand WWOX in epithelial ovarian carcinomas and their relations with clinicopathological and other molecular parameters.To help determine whether the expression of the genes FHIT and WWOX are associated with EOC progression and metastasis.Methods:1,With reference to the expression ofβ-actin,the expressions of FHITmRNA and WWOXmRNA in epithelial ovarian carcinomas and normal ovarian epithelial tissues were determined by reverse transcription-polymerase chainreaction(RT-PCR),and semi-quantification of band densities was also performed.The expressions of estrogen receptor(ER) and progesterone receptor(PR) in the 48 ovarian cancer lesions were detected by immunohistochemical method.The relationship between the expressions of the genes and the prognosis of patients was also studied..2,Immunohistochemistry SP method was performed to examine the expression level of FHIT and WWOX in normal ovary tissues and various grades of primary and metastatic EOC.Comparisons were made between expression patterns in normal ovary and EOC.The expression of FHIT and WWOX among groups were initially compared by x² analyses and Fisher exact probabilities test.Results:1,19 and 15 cases of epithelial ovarian carcinomas(39.6%and 31.3%) showed respectively loss or absence of WWOX and FHIT genes,but there was no loss of WWOX and FHIT genes in normal ovary tissues.The expressions of FHITmRNA and WWOXmRNA in 48 epithelial ovarian tumors were correlative(P＜0.05),but were not related with patients' ages,tumor histologictype,ER,metastasis and ascites.The expression of WWOXmRNA was related to PR(P＜0.05).There was reverse correlation between the expressions of FHIT and WWOX and the clinical stages.In addition,WWOX was closely connected with the prognosis of patients.2,The study revealed a close relationship between tumor phenotype and FHIT and WWOX expressionlevels,characterized by high expression in normal ovary,while low expression(27/48,25/48) in primary invasive and metstatic tumors. Statistically siginificant differences were noted between normal ovary and EOC(P＜0.05).The statistical evaluation showed that decrease of FHIT and WWOX expression was associated with the advanced stage of EOC(P＜0.05).It also revealed an inverse relationship between histological grade and FHIT and WWOX(P＜0.05).The statistical evaluation also showed that the expression of FHIT and WWOX had a correlation with lymph node metastasis(or distant metastasis)(P＜0.O5).There is no significant relationship among FHIT and WWOX expression and age and tumor histologic type(P＞0.05).The expressions of FHI Tand WWOX in 48 epithelial ovarian tumors were correlative(P＜0.05).Conclusions:1.FHIT and WWOX expression are closely correlated with the malignant progression and metastasis.It may be an early event in the progression of this tumor.Detecting the expression of FHIT and WWOX probably possesses clinical significance in evaluating the differentiation,tumor progression and predicting the prognosis.2.The expressions of FHIT and WWOX in 48 epithelial ovarian tumors are related with the advanced stage of EOC and lymph node metastasis(or distant metastasis),but no relationship with patients' ages,tumor grades,tumor histologic type.