| Ovarian cancer is one of three malignant tumors of female reproductive system. Due to lack of early diagnostic methods, high recurrence rate and drug resistance after recurrence, the therapeutic effect is not very well. Therefore it becomes the key points for increasing the survival rate of ovarian cancer that how to doing early diagnosis and overcoming recurrence and drug resistance.Cancer Stem Cells (CSCs) are residing in tumor tissues and few in amount. CSCs possess the potentials of boundless proliferation and differentiation to tumor cells. Moreover, they determine tumor genesis, development and metastasis, also are the reasons of tumor recurrence, metastasis and treatment failure. The theory of ovarian cancer stem cells provides the new targets to diagnosis and therapy of ovarian cancer, however, selection of surface markers of ovarian cancer stem cells has become the precondition of early diagnosis and healing. So it has great significance that identifying the specific genes of CSCs from tumor expression profiles and using them as biological tags to evaluate the prognosis and survival of patients. At present, little research is on the ovarian cancer stem cells and its specific markers are not be found. The CSCs have similar surface markers with normal stem cells, so we can use the surface markers of normal stem cells, such as CD133, to screen markers of CSCs. Also Lgr5 which has a close relation with primary tumor as colon carcinoma probably become the key target for future oncotherapy.To sum up, we used 33 cases of ovarian papillary serous adenocarcinoma as research objects and 6 cases of normal ovarian tissue and 6 cases of ovarian serous cystadenoma as control to detect the expression of Lgr5 and CD133, stem cell markers, by immunohistochemistry staining. To investigate its relationship with tumor progression and clinical pathological parameters, discuss the correlation between the expression of Lgr5 and CD133 and then provide the theoretical and experimental basis on targeted therapy of ovarian cancer by tumor stem cells. The experimental results are as follows: 1,The expression of Lgr5 on ovarian cancerThe results of immunohistochemistry staining showed that Lgr5 was brown yellow granules and mainly expressed in the cytoplasm. In normal ovarian tissue, Lgr5 was expressed in follicular cells, vessel wall and stroma. Its positive rate was 33.3% and all were weak expression. In cases of ovarian serous cystadenoma, positive rate of Lgr5 expressed in the cytoplasm of tumor cells was 33.3% and there was no difference with normal ovarian tissue (P>0.05). In cases of ovarian cancer, Lgr5 was expressed in tumor cells, positive rate was 78.7% and 3 cases were strong expressed. The expression of Lgr5 in ovarian cancer had significant difference compared with normal ovarian tissue or with ovarian serous cystadenoma (P<0.05). In addition, the expression of Lgr5 was not equal in cases of ovarian cancer, which showed that Lgr5 was expressed strongly in parts of tumor cells in one field and positive rates of Lgr5 were also different with the degree of tumor differentiation, in another words the expression rate of Lgr5 was gradually increased with tumor differentiation from high to low. The results suggested that the expression level of Lgr5 was gradually upregaulated with the increasing of tumor malignant degree and Lgr5 was related with tumor genesis and progression. Moreover, there was no correlation between the expression level of Lgr5 and clinical pathological parameters, such as age and lymph node metastasis (P>0.05).2,The expression of CD133 on ovarian cancerCD133 was mainly expressed in the cytoplasm and shown brown yellow granules. In normal ovarian tissue, the expression of CD133 was weak and positive rate was 33.3%. In cases of ovarian serous cystadenoma, positive rate of CD133 expressed in the cytoplasm of tumor cells was 50% and there had significant difference compared with normal ovarian tissue (P<0.05). In cases of ovarian cancer, positive rate of CD133, expressed in nuclei and cytoplasm of tumor cells, was 57.5% and there was significant difference compared with normal ovarian tissue(P<0.05), however no difference with ovarian serous cystadenoma(P>0.05). Also we found the expression of CD133 was very strong in the edge of ovarian carcinoma nest, which implied that CD133 positive tumor cells had more strong ability of invasion. Moreover, the expression level of CD133 was gradually increased with reduce of tumor differentiation degree. The results indicated that the expression level of CD133 was related with tumor genesis and progression. However, the expression of CD133 was not correlated with the clinical pathological parameters, for example, the age and lymph node metastasis (P>0.05).3,The correlation between the expression of Lgr5 and CD133Up to now, there was no report on the correlation between the expressions of Lgr5 and CD133 in ovarian cancer. However by the correlation analysis, we found in ovarian cancer that 6 cases was no expression of Lgr5 and CD133 and 18 cases were co-expression of them, also there were 8 cases of Lgr5+ CD133- and one case of Lgr5-CD133+.Thus there was positive correlation between the expression of Lgr5 and CD133 in ovarian cancer (r=0.71,P<0.01), which meant the expression of CD133 was increased with the up-regulation of Lgr5.We got the conclusions based on those experimental results, that the expressions of Lgr5 and CD133 were associated with the tumor genesis and development, then detection of Lgr5 and CD133 in different pathological stages of ovarian carcinoma will contribute to diagnosis and assessment of prognosis to ovarian cancer. So it is possible for Lgr5 and CD133 to work as surface markers of ovarian serous papillary adenocarcinoma stem cells. |
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