The Expression Of Slit2/Robol In Breast Tumor And Their Relationship To Brain Metastasis

ObjectiveBreast cancer is one of malignant tumors that damages omen's health seriously。The rising incidence of disease and Incidence younger trend, make the breast cancer in many big cities having grown to be the first female malignant tumors. Breast cancer metastasis are led to treatment failure and the important reasons for the patients died, Data suggest 10%～16% breast cancer patients will appear brain metastases, and the prognosis is poor. Current research shows that neural axon guidance protein 2 (Slit2) relates to multiple tumors, this study discussed Slit2/ Robo1 protein levels with the correlation of brain metastases from breast cancer, and analyses its relationship to many clinical pathologic index.MethodsImmunohistochemical study for Slit2 and Robol were performed on 24 cases of invasive ductal carcinoma(IDC) with brain metastsis,71 cases of IDC without brain metastsis,22 cases of ductal carcinoma in situ(DCIS) and 23 cases of adenofibroma using LSAB methods. The relationship between Slit2, Robo1 and various pathologic parameters (estrogen and progesterone receptor status, Her2/neu status, age, histologic grade, pathologic stage,lymph node metastasis and prognosis etc.) in breast tumor was analyzed. In addition, we select 21cases of breast cancer metastasizing specimens by neurosurgery,10 of which are metasis from Previously mentioned breasr cancer patients, to detect the expression of Slit2 and Robo1, analyzes their expression changes before and after the metastsis. We further analysis the correlation of Slit2 and Robo1 to breast cancer brain metastsis.ResultsSlit2 was mainly expressed in the plasma of tumor cells. The expression level of Slit2 in IDC(48%) and DCIS (59%) was significantly lower than that in adenofibroma(87%), P<0.05. The expression of Slit2 was significantly higher in more than 50 yesr-old-group(62%) than in less than 50 year-old-group(34%) of IDC patients, and highly related with the duration of IDC patients, P<0.05. No correlation was found between the Slit2 expression and the tumor size,lymph node metastasis, pathologic stage and histological grade, P>0.05.2. Robol was mainly expressed in the plasma of tumor cells. The expression level of Robol in IDC(44%) and DCIS (59%) was significantly lower than that in adenofibroma(87%), P<0.05. The expression of Robol was significantly higher in more than 50 yesr-old-group(58%) than in less than 50 year-old-group(34%) of IDC patients, and highly related with the duration of IDC patients, P<0.05. No correlation was found between the Robo1 expression and the tumor size, lymph node metastasis, pathologic stage and histological grade, P>0.05.3. The expression level of Slit2/Robol as+/+was 41 cases(35%),-/-was 48 cases(41%),+/-was 4 cases(3%),-/+was cases(2%)in IDC, they have high correlation, P<0.05.4. The expression level of Slit2/Robo1 in IDC with brain metastasis (13%) was significantly lower than that in IDC without brain metastasis (59%),(P<0.05). The expression of Slit2 was highly correlated with that of Robol in both breast cancer and brain metastasis tissue. Slit2 and Robol are negativeiy expressed in each breast cancer brain meatstasis tissue we studied.5. Univariate Kaplan-Meier survival analysis reveals that patient with Slit2-and Robol-showed lower survival rates than those with Slit2+and Robol+, P<0.05.Conclusion1. The expression of Slit2/Robo1 has high correlation, Robo1 is Slit2 receptor. Both of their expression rate is decreased in breast neoplasms, and the expression rate in breast cancer is much significantly lower than that in adenofibroma, it displays that Slit2/Robol play an important role in the development process of breast cancer.2. The expression rate of Slit2/Robo1 in breast cancer brain metastasis is obviously lower than that in breast cancer without brain metastasis, and there's no positive expression in the metastatic specimen get from IDC patients, indicates Slit2/Robol plays an important role in the process of inhibiting breast cancer brain metastasis.3. The Slit2/Robo1 expression correlates positively with the age and duration of IDC patients. They would be applied as a marker in evaluating the IDC invasiveness and brain metastasis, and would be a new therapeutic target. 4. Lost expression of Slit2/Robol is one of the important factors for breast cancer and brain metastases, it provides new basic theory for indiidual therapy of breast cancer and brain metastasis.