Expression And Significance Of Wnt1 And Lgr5 In Epithelial Ovarian Cancer Tissue

Objective: Ovarian cancer is one of the three common malignant tumors of female productive organs. Epithelial carcinoma is the most common histological type, accounting for 85%-90% of the ovarian malignant tumors. Its morbidity has just ranked after cervical cancer and endometrial cancer. However, its mortality rate is the highest in gynecological malignancies. Thus, ovarian cancer has become a serious threat to women’s healthy and lives. Due to lacking of symptoms and efficient early diagnostic methods, most of the ovarian cancer patients can not be diagnosed until they are at the advanced stage. Because of high recurrence rate and chemotherapy resistance, the five-year-survival rate of the patients with ovarian cancer is still below 30%. Thus, the solution of early diagnosis, recurrence and chemotherapy resistance issues are the keys to improve the prognosis of these patients.Ovarian epithelial cancer(EOC) belongs to a heterogeneous group of tumors, of which tissue type of origin is uncertain. Cancer Stem Cells(CSC) Hypothesis is a new theory proposed in recent years, which considers that Cancer Stem Cells is a class of cell subsets presented in the tumor tissue, with self-renewal, unlimited proliferation and multi-differentiation potency of stem cell properties. Though the amount of it is very few, it is the root cause of tumor growth, metastasis, recurrence and chemotherapy resistance. Wnt signaling pathway is involved in embryonic development, regulates cell proliferation, differentiation, movement and apoptosis which is closely related to the regulation of stem cells and the tumor development. It is a complex system involved in a variety of molecules and mutual influence. Wnt1 gene is the first proto-oncogene which is discovered in Wnt gene family, and it is also an important participant in Wnt signaling pathway activation. Lgr5, also known as GPR49 which is a targeted gene of the Wnt signaling pathway, is a new member of the G-protein coupled receptor family. Lgr5`s expression scatters in many normal human tissues such as brain, spinal cord, hair follicles, gastrointestinal and reproductive organs. In recent years, studies have found that Lgr5 can be used as a stem cell marker in variety of adult tissues, and its over-expressed in a variety of tumor tissues, a potential marker of cancer stem cells. Therefore, Lgr5 may be a potential marker of cancer stem cells.Currently, the reports about Wnt1 and Lgr5 in Ovarian epithelial cancer(EOC) are few. In this study, Immunohistochemical method was used to combined detection the expression of Wnt1 and Lgr5 protein in epithelial ovarian tumor tissues, and this study explored their relationship with clinical pathological characteristics, as well as the correlation between them. It tries to provide a new theoretical basis for the diagnosis, treatment and the prognosis of EOC.Methods: Immunohistochemical(IHC) method of PV was used to examine for the expression of Wnt1 and Lgr5 protein in 18 cases of normal ovary tissue, 18 cases of benign ovarian epithelial tumor tissue, 38 cases of EOC tissue and study their relationship with different clinical pathological features and the correlation between the expression of them in EOC tissue. SPSS17.0 statistical software was used to analyze database and the correlation analysis. Count data was analyzed by Pearson’s Chi-square test or Fisher Exact test and the correlation between two rank variables was analyzed by Spearman rank correlation analysis. All the tests were two-sided with α=0.05 as the inspection level. P<0.05 is considered to be statistically significant difference.Results:1 Wnt1 protein was mainly expressed in cytoplasm and Lgr5 protein was mainly expressed in cytoplasm and(or) membrane. Both of them were brown yellow granules. In normal ovarian tissue, Wnt1 and Lgr5 protein were mainly expressed in epithelial cells and both of their positive rates were 11.1%. In benign ovarian epithelial tumor tissue, Wnt1 and Lgr5 protein were expressed in the tumor cells and their positive expression rates were 81.6% and 76.3% respectively. In EOC tissue, Wnt1 and Lgr5 protein were expressed in the cancer cells and the positive expression rates were 81.6% and 76.3% respectively. According to the comparison of the positive rates of Wnt1 and Lgr5 protein among the three groups, we can see that the differences were statistically significant(P<0.05). The positive rates of Wnt1 and Lgr5 protein in EOC tissue were significantly higher than those in normal tissue and benign tumor tissue and the differences were statistically significant. However, the differences among the expression of Wnt1, Lgr5 protein in normal tissue and benign tumor tissue were not significant(P>0.05).2 The expression of Wnt1 and Lgr5 protein had no significant correlation with the tumor histologic type. But they were closely correlated with the tumor differentiation grade, pathological stage and lymph node metastasis(all P<0.05). The positive expression rates of Wnt1 and Lgr5 protein in serous adenocarcinoma, mucinous cystadenocarcinoma, endometrial carcinoma and clear cell carcinoma tissues were 90.9%/86.4%, 75.0%/66.7%, 50.0%/50.0% and 50.0%/50.0% respectively. The differences among the four groups were not statistically significant(P>0.05). The positive rates in well and moderate differentiated carcinoma tissue were 62.5% and 50.0% respectively, while the rates in low differentiated carcinoma tissue were both 95.5%. The differences between them were statistically significant(P<0.05). The results suggest that the expression level of Wnt1 and Lgr5 protein were gradually increased along with the progress of malignant grade. The positive rates in early EOC(Ⅰ/Ⅱ) tissue were 53.8% and 46.2% respectively, while the rates in advanced EOC(Ⅲ/Ⅳ) tissue were 96.0% and 92.0% respectively. The differences were significant(P<0.05). The positive rates in EOC tissue with lymph node metastasis group were 95.7% and 91.3% respectively, while the rates in those tissues without lymph node metastasis group were 60.0% and 53.3% respectively. The differences were statistically significant.3 From the correlation analysis, we found that the expression of Wnt1 and Lgr5 protein in EOC tissue had a significant consistency and the relationship between them was positive(rs=0.534, P<0.05).Conclusions:1 Wnt1 and Lgr5 protein are both highly expressed in epithelial ovarian cancer tissue. It indicates that Wnt signaling pathway may be involved in the development of epithelial ovarian cancer.2 The expression of Wnt1 and Lgr5 protein may play important roles in tumor differentiation, tumor stage and lymph node metastasis of epithelial ovarian cancer. It indicates that Wnt1 and Lgr5 may play an important role in the development, invasion and metastasis of epithelial ovarian cancer.3 The expression of Wnt1 and Lgr5 protein indicates that both of them may play a synergistic role in the development and progression of epithelial ovarian cancer.