Expression And Implication Of Survivin, FHIT And BFGF In Cervical Squamous Cancer

Background and ObjectiveCervical cancer, the morbidity of which is just secondary to breast cancer, is the most common female genital malignant tumor and a deadly disease that threats women's health. In recent years, the incidence of cervical cancer tends to be significantly higher and the sufferers tend to be younger. Since it has been seriously threatening masses of women's health, therefore, a study of its etiology and pathogenesis is rather necessary and important. Despite of the complexity of genetic changes and multiple factors, cell proliferation and the abnormal regulation of apoptosis are the ubiquitous factors to the occurrence of cervical cancer, of which the loss of tumor suppressor gene function and expression of oncogenes can lead to a series of pathological changes in the cervical tissue and cause the abnormal regulation of cell proliferation and apoptosis, which will eventually result in tissue cancerization. Therefore, finding molecular markers that can be used to suggest cervical cancer pathogenesis from the molecular level is of significant importance to the early diagnosis and treatment of cervical cancer.Survivin is an effective apoptosis inhibitor discovered currently. The survivin protein of this gene expression is by far the most powerful anti-apoptosis inhibitor of apoptosis protein with the minimum molecular weight. Survivin possesse the dual functions of cell cycle control and apoptosis inhibition. The excessive expression of Survivin protein in various malignant tumors is closely related with the incidence, invasion and prognosis of tumor. Research shows that Survivin protein has no expression in normal cervical tissue, but low expression in cervical intraepithelial neoplasia (CIN) and excessive expression in cervical cancer, which have been confirmed by immunohistochemistry. Survivin protein is closely related with the prognosis and metastasis of cervical cancer. However, the relationship between the complex function and subcellular localization has not been elucidated.FHIT gene was a new candidate tumor suppressor gene found in 1996. FHIT protein of FHIT gene encoding is a typical two adenosine triphosphate hydrolysis enzyme (diadenosine-triphosphate hydrolase, Ap3A). And the specific function of Fhit protein in vivo is still unclear. Currently, studies on the mechanism of its inhibition of tumor mechanism are mainly focused on cell cycle control and and cell apoptosis. At present, research on FHIT gene at home mainly includes lung and gastrointestinal tumor, head and neck tumor. However, research on cervical cancer is rare seen.bFGF is an important factor of cell growth, differentiation and angiogenesis. bFGF, a cancer-related peptides, involves in the formation of malignant tumor by promoting cancer cell proliferation, migration differentiation and angiogenesis and is the most effective factor in promoting tumor angiogenesis. The relationship between bFGF and tumor has been a hot spot concerned by researchers in recent years.The expressions of survivin, FHIT and bFGF in tumor have already been studied. However, at present there is still no joint report on the study of survivin, FHIT and bFGF in cervical cancer in the literature both at home and abroad. This study detects paraffin-embedded cervical cancer, cervical intraepithelial neoplasia (CIN) and the expressions of survivin, FHIT and bFGF in normal cervical tissue with immunohistochemical technology and probes into the mechanism of them in the occurrence, development and metastasis of cervical cancer. Hope that this study can provide effective clinical guidelines for the early diagnosis and treatment of cervical cancer and open up a new way to the gene therapy for cervical cancer. Material and Methods1.experimental groupThe specimens were collected from the surgical removal in the Second Affiliated Hospital of Zhengzhou University from January,2008 to November,2009. There were 45 cases of cervical squamous cancer tissues that were surgically removed and pathologically confirmed,45 cases of cervical intraepithelial neoplasia(CIN) and 15 cases of normal cervical tissues.2.experimental techniqueStreptavidin perorxidase immunostaining technique was used to examine the expression of survivin, FHIT and bFGF in cervical squamous cancer tissues, cervical intraepithelial neoplasia (CIN) tissues and normal cervical tissues.3. Statistics analysisAll of the statistical analysis was performed with package SPSS version 17.0 software. The comparison between groups was assessed by chi-square test and the correlation was analyzed through Pearson. P<0.05 was considered as statistically significant.Rusults1. Survivin's expressions in different cervical tissuesSurvivin tended to increase in the expressions of normal cervical tissues, cervical intraepithelial neoplasia (CIN) tissues and cervical squamous cancer tissues. The expression rate in normal cervical tissues was much lower than that in CIN(x2=7.273 P<0.05) and cervical squamous cancer tissues(x2=22.857 P<0.05). The difference between CIN and cervical squamous cancer tissues was statistically significant (x2=11.429 P<0.05). The expression of survivin was notably correlated with clinical stages and pathological grading (P<0.05) and the correlation with lymph node metastasis was not notable (P>0.05)2. FHIT's expressions in different cervical tissuesThe positive expression rates of FHIT in normal cervical tissues, cervical intraepithelial neoplasia(CIN) tissues and cervical squamous cancer tissues showed a decreasing tendency. The positive expression rate of survivin in normal cervical tissues was significantly higher than that in cervical intraepithelial neoplasia (CIN)tissues(x2=8.571 P<0.05)and cervical squamous cancer tissues(x2=22.857 P<0.05). There were also significant differences between CIN and cervical squamous cancer tissues(x2=8.820 P<0.05). The expression of FHIT in cervical squamous cancer was not notably correlated with t clinical stages and pathological grading, but was significantly correlated with lymph node metastasis (p<0.05)3. bFGF's expressions in different cervical tissuesbFGF tended to increase in the expressions of normal cervical tissues, cervical intraepithelial neoplasia (CIN) tissues and cervical squamous cancer tissues. The difference between the expression in normal cervical tissues and that in CIN was not statistically significant (x2=1.452 P>0.05). There was significant differences between the expression in normal cervical and that in cervical squamous cancer tissues (x2=11.769 P<0.05). The difference between CIN and cervical squamous cancer tissues was also statistically significant (x2=11.429 P<0.05). The expression of bFGF was significantly correlated with clinical stages, pathological grading and lymph node metastasis (P<0.05).4. The correlation between survivin,FHITand bFGF in cervical cancer Through an analysis of table 3.4, we can see that the expression of survivin and FHIT were significantly correlated (r=-0.675, P<0.05), whereas the correlation with the expression of bFGF was not significant (r=0.039, P> 0.05). The expression of FHIT and bFGF were not significantly correlated (r=0.071, P>0.05).Conclusions1. survivin,FHIT and bFGF paly important roles in the occurrence and development of cervical cancer.2. FHIT and bFGF are relevant to the invasion and metastasis of cervical squamous cancer3. Survivin and bFGF show synergistic effect in the development of cervical squamous cancer...