Expressions And Significance Of Focal Adhesion Kinase And Deleted In Liver Cancer-1 In Epithelial Ovarian Cancer Tissues

Background and objectiveOvarian cancer is one of the most common malignant tumors in female genital system, the mortality rate ranks first in gynecological malignancies. Because of a lack of obvious early symptoms, most of the patients with ovarian carcinoma present with widespread metastatic disease at the time of diagnosis.There is no effective diagnosis so far.So, the focus and emphasis of research is to find highly effective and safe therapy and target, and to extend the life expectancy and to improve the quality of life in patients with ovarian cancer.Focal adhesion kinase is a nonreceptor tyrosine kinase, a point of convergence in the action of neuropeptides, intergrins and oncogenes.FAK mediated signal transduction plays an important role in the pathogenesis, development, invasion and metastasis of tumors. Studies have shown that FAK overexpression or elevated activity has been demonstrated in the tumors of various origins.FAK may become a novel target for ovarian cancer therapeutics. DLC-1 is an important tumor suppressor gene, which is underexpressed or absent in many kinds of human tumors.DLC-1 is able to inhibit tumorigenesis, invasion and metastasis, and plays an important role in detecting and predicting the recurrence,metastasis and prognosis of ovarian cancer.This study respectively detected the expression of FAK and DLC-1 protein in 22 patients with normal ovaries and 62 patients with ovarian carcinoma; the expression of FAK and DLC-1mRNA in 12 patients with normal ovaries and 32 patients with ovarian carcinoma by immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR)methods, analysed their correlations and the relations between their expressions and the clinicopathological features. We want to identify the role of FAK and DLC-1 in the generation and development of ovarian cancer, and further understand the molecular biological mechanism of ovarian cancer, and provide theoretical and experimental basis to diagnosis and therapy of ovarian cancer with FAK and DLC-1.Materials and Methods1 44 cases of ovarian tissues keeping in the Department of Obstetrics and Gynecology, The First Affiliated Hosipital of Zhengzhou University from January 2007 to October 2008 were included in this study, which consisted of 32 cases of epithelial ovarian cancer, and 12 cases of normal ovarian tissuses. At the same time 40 cases of ovarian tissues keeping in the archives in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University from 2006 to 2007 were included in this study, which consisted of 30 cases of epithelial ovarian cancer, and 12 cases of normal ovarian tissuses.2 Immunohistochemistry was used to detect the expression of FAK and DLC-1 at the protein level in paraffin specimens from 22 patients with normal ovaries and 62 patients with epithelial ovarian cancers.3 RT-PCR method was used to detect the expression of FAK and DLC-1mRNA in 12 patients with normal ovaries and 32 patients with epithelial ovarian cancers.4 Analysing their correlations between FAK and DLC-1, and the relations with their clinical pathological characters of epithelial ovarian cancer.5 Statistical analysis:The SPSS statistical package porgrma 13.0 was used for all analysis.Measurement data were tested by t test and One-Way ANOVA; Count data were tested byχ2 test and FISH exact probability; The correlation analysis was analyzed by Pearson and Spearman correlation test. a=0.05 was considered as the test standard.Results1 The positive rate of FAK protein expression in epithelial ovarian cancer and normal ovary were 79.0% and 32.0% respectively,the expression in epithelial ovarian cancer is obviously higher than that in normal ovarian,there is statistical difference (P<0.05).The positive rate of DLC-1 protein expression in epithelial ovarian cancer and normal ovarian tissues were 54.8% and 100% respectively,the expression in epithelial ovarian cancer is obviously lower than that in normal ovarian tissues,the difference is statistically significant (P<0.05).2 The relative expression level of FAKmRNA in epithelial ovarian cancer and normal ovarian were 0.81±0.33 and 0.24±0.15 respectively,the relative expression level of FAKmRNA in epithelial ovarian cancer was significantly higher than that in normal ovarian tissues, the difference is statistically significant (P<0.05);The relative expression level of DLC-1mRNA in epithelial ovarian cancer and normal ovarian were 0.30±0.11and 0.68±0.17 respectively,the relative expression level of DLC-1mRNA in epithelial ovarian cancer was significantly lower than that in normal ovarian tissues, the difference is statistically significant (P<0.05).3 The positive rate of FAK protein expression in G1, G2 and G3 grade of epithelial ovarian cancer were 60.9% and 89.7% respectively, the expression in the groups with lymph node metastasis and without lymph node metastasis were 95.8% and 68.4% respectively, The positive rate of FAK protein expression in the patients with ascites and without ascites were 89.1% and 50.0% respectively, differences between groups were statistically significant (P<0.05). The positive rate of DLC-1 protein expression inⅠ-ⅡandⅢ-Ⅳstage of epithelial ovarian cancer were 75.0% and 45.2% respectively, the expression in the groups with lymph node metastasis and without lymph node metastasis were 33.3% and 68.4% respectively, The positive rate of DLC-1 protein expression in the patients with ascites and without ascites were 26.1% and 62.5% respectively, differences between groups were statistically significant (P<0.05).4 The relative expression level of FAKmRNA in G1,G2 and G3 grade of epithelial ovarian cancer were 0.50±0.24,0.79±0.38 and 0.90±0.29 respectively,the relative expression level of FAKmRNA in the groups with lymph node metastasis and without lymph node metastasis were 0.94±0.22 and 0.71±0.38 respectively, the expression in the patients with ascites and without ascites were 0.90±0.32 and 0.62±0.30 respectively, differences between groups were statistically significant (P<0.05); The relative expression level of DLC-1mRNA inⅠ-ⅡandⅢ-Ⅳstage of epithelial ovarian cancer were 0.38±0.02 and 0.26±0.12 respectively,the relative expression level of DLC-1mRNA in the groups with lymph node metastasis and without lymph node metastasis were 0.26±0.18 and 0.36±0.07 respectively, the expression in the patients with ascites and without ascites were 0.24±0.05 and 0.33±0.11 respectively, differences between groups were statistically significant (P<0.05).5 Expressions of FAK mRNA and protein were negative correlated with expressions of DLC1mRNA and protein. (r=-0.396, P= 0.025; r=-3.08, P= 0.015).Conclusions1 The overexpression of FAK and the underexpression or close of DLC1 may play an important role in the generation and development of epithelial ovarian cancer.the combination determination of FAK and DLC1 expression level may be helpful in predicting the maligant degree.2 The positive expression of FAK mRNA and protein were related with grade,ascites formation and lymphatic metastasis,The underexpression of DLC1mRNA and protein were related with clinical stage,ascites formation and lymphatic metastasis,FAK and DLC-1 can be used as ovarian cancer survival and prognosis and the combination determination of FAK and DLC1 expression level may be helpful in predicting the maligant degree.