| Background and ObjectiveOvarian cancer is the leading fatal cause of death among gynecological cancers with a 5-year survival rate close to 30%. The etiology of ovarian cancer is still unclear. The development and progression of ovarian cancer is a multistep process, which involves many factors, such as abnormal activation in oncogene, loss of function in tumor suppressor gene and alteration in DNA repair gene. Fragile histidine triad gene(FHIT) is a tumor suppressor gene. Reduced or absent FHIT protein expression has been reported in approximately sixty percent of epithelial cancers, such as lung cancer, cervical cancer, breast cancer, etc. These abnormalities in FHIT protein expression of many kinds of tumors have been found to be correlated with poor outcome of some patients. However, the role of FHIT gene in ovarian cancer is controversy. The aberrated ratio of cell proliferation and apoptosis is a vital mechanism that lead to the development of cancer. Ki67 is a cell proliferation nuclear antigen, which is recognized as the most ideal marker reflecting cell proliferation level. The purpose of the study is to definethe role of fragile histitine triad (FHIT) and Ki67 genes during evolutionof the primary epithelial ovarian tumor.MethodsThe expression of FHIT,Ki67 proteins was evaluated on formalin fixed, paraffin-embedded, archival specimens of primary ovarian epithelial tomors(malignant n =40,borderline tumor n=20,benign adenoma n=20) from patients undergoing surgery by Envision and streptoavidin peroxidase conjugated(SP) immunohistochemistry. The relationship between the expression of FHIT, Ki67 protein and clinical pathological parameters such as FIGO stage, histotype and that of the expression of FHIT and Ki67 protein were analysed. Results1.The expression rate of FHIT protein in PEOC, ovarian borderline tumor, ovarian benign adenoma was 65%(26/40), 95%( 19/20) and 100%(20/20), respectively. The expression rate of FHIT protein in PEOC was significantly lower than that in ovarian borderline tumor and ovarian benign adenoma. There was no significant difference between the expression of FHIT protein in ovarian borderline tumor and that in ovarian benign adenoma. The expression rate of FHIT protein was significantly lower in ovarian serous cancer than that in nonserous ones. There were all positive expressions of FHIT protein in ovarian mucinous and endometrioid cancer. The expression of FHIT protein was significantly correlated with differentiated grade, FIGO stage and lymph node metastasis (p <0.05). The expression of FHIT protein was not correlated with the diameter of residual tumors(p >0.05).2. Ki67 protein was detected positive(Ki67 PI>20%) in 65%(26/40) ofthe epithelial ovarian cancers, but in none of the ovarian borderline tumors and ovarian benign adenomas. The expression rate of Ki67 protein in PEOC was significantly higher than that in ovarian borderline tumor and ovarian benign adenoma. There was no significant difference between the expression of Ki67 protein in ovarian borderline tumor and that in ovarian benign adenoma. The present data demonstrated that the expression of Ki67 protein in epithelial ovarian cancer was significantly correlated with FIGO stage, histological grade, lymph node metastasis (p<0.05). Howerver, the expression of Ki67 protein was not correlated with different histological classifications and the volume of residual tumors (p>0.05) .3.A significantly inverted relationship was observed between FHIT and Ki67 protein expression in primary epithelial ovarian cancer(Spearman Rank Coefficience, r,=-0.543, p<0.05). Conclusions1 .The results suggest that loss of FHIT protein expression may be an important event in carcinogenesis and evolution of the epithelial ovarian cancer, which may be dependent on cell hyperproliferation.2. The expression of Ki67 protein is correlated with FIGO stage, histologic grade and lymph node metastasis, which indicates cell hyperproliferation is an important mechanism during the evolution of the ovarian cancer.3. There is a significantly inverted relationship between the expression of FHIT protein and that of Ki67 protein .The combinatory detection of FHIT and Ki67 protein expression may be helpful to decern the poorer prognostic patient. |
