The Clinical Calue Of Urine CD105 Level In Monitering Recurrent And Metastatic Breast Cancer

Objective:CD105 was also named as Endoglin, which was a glycoprotein expressed on the endothelial cells, and its main function was involved in angiogenesis, and it was highly expressed on the tissue with new vascular formating. It had been confirmed that the serum CD105 level will increase when recurrence or metastasis happened and decrease when given chemotherapy. However, there had not been any study on the relationship between the urine CD105 level and the progression of the disease. Our investigation mainly detected the level of urine CD105 of patients with recurrent or metastatic breast cancer by enzyme-linked immunosorbent assay(ELISA). And then made comparison with serum CEA and CA15-3 level of the patients in the corresponding period. We also compared the urine CD105 level among different recurrent or metastastic sites, different pathology and different expression status of Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor recepter-2(HER-2). We hoped to find a new marker for the early diagnosis, evaluation of the treatment and prognosis in the recurrent or metastatic breast cancer.Methods:We selected 40 recurrent or metastatic breast cancer patients containing 24 with distant metastasis and 16 with local recurrence (including 8 chest wall recurrence and 8 ipsilateral regional lymphnode metastasis). They were reinspection or rehospitalization in the Fourth Hospital of Hebei Medical University during Mar.2009 to Dec.2010. We also selected 20 postoperative breast caner patients without recurrence or metastasis and 15 healthy subjects as control. We detected the urine CD105 level by ELISA in every patient, and we aslo detected the serum CEA and CA15-3 level by electrochemiluminescence in the patients with recurrence or metastasis. We compared and analysed the level of the urine CD105 and serum CEA and CA15-3. We aslo analysed the urine CD105 level bewteen different recurrent or metastatic sites, different primary pathology and different ER, PR and HER-2 status. We use median (range) for the concentration of urine CD105 and SPSS13.0 (SPSS Company, Chicago, Illinois, USA) for statistical analysis. We use Non-paramentric test for the comparison of urine CD105 concentration in our study, Kruskal-Wallis Test among groups and Mann-Whitney Test between every two groups. We compared the positive rate of urine CD105, serum CEA and serum CA15-3 with Pearson Chi-Square Test. We sent the test level of =0.05, P=0.05 as statistically significant.Results:1 The median concentration of the urine CD105 in the recurrence or metastasis group, no recurrence or metastasis group and the health control group was 50.62pg/ml(19.17~411.79pg/ml), 29.70pg/ml(4.78~129.55pg/ml) and 31.44pg/ml(17.06~48.26pg/ml) respectively. They were statistically different (X~2=8.922; P=0.012). With further analyzation, we find that the urine CD105 level of recurrence or metastasis group was higher than that of the grorp with no recurrence or metastasis (Z=-2.486; P=0.005). And it was also higher than the health control group (Z=-2.315; P=0.010). But there was no statistical difference between the group without recurrence or metastasis and the health control group(Z=-0.333; P=0.739).2 According to the standard of the 95% concentration of the urine CD105 in the health control group, we defined it negative(-) when the urine CD105 level was blow the standard and positive(+) opposite. We defined negative(-) when serum CEA<5ng/ml, CA-153<25U/ml as it was given in the CEA, CA-153 kit, and positive(+) opposite. We defined it positive(+) as long as any of the items was positve(+) when we detected the items jointly. We find that the positive rate of the urine CD105, serum CEA and serum CA15-3 in the postoperative recurrence and metastasis group was 45%, 35% and 40% repectively. There were no statistical difference among the three groups (X~2=0.833; P=0.659). There was no statistical difference between every two items of the urine CD105, serum CEA and serum CA15-3 either (X~2=0.833; P=0.361), (X~2=0.205; P=0.651), (X~2=0.213; P=0.644). The joint positive rate of the serum CEA and serum CA15-3 was 50%, and there was no statistical difference when it was compared with urine CD105 (X~2=0.201; P=0.654).With further study, we find that the joint positive rate of the urine CD105, serum CEA and serum CA15-3 was high to 70%, and it was higher than the positive rate of every single one of the three indicators (X~2=5.115; P=0.021),(X~2=9.825; P=0.002), (X~2=7.273; P=0.006).3 According to different recurrent or metastatic sites, we divided the patients with recurrence and metasitasis into 6 groups: 8 with ipsilateral regional lymph nodes metastasis, 8 with chest wall recurrence, 5 with visceral metastasis, 5 with osseous metastasis, 11 with multiple metasta-sis and 3 with other sites metastasis. The median concentration of the urine CD105 was 79.49pg/ml(15.75~134.22pg/ml), 30.08pg/ml(18.00~53.74pg/ml), 24.56pg/ml(14.49~65.00pg/ml), 185.43pg/ml(24.45~411.79pg/ml), 44.53pg/ml(19.17~265.98pg/ml) and 25.54pg/ml(20.64~81.63pg/ml) resp-ectively, and there was no statistical difference among the 6 groups (X~2=9.771; P 0.082). But we find that the urine CD105 level of the ipsil-ateral regional lymph nodes metastasis group was higher than that of t-he visceral metastasis group and chest wall recurrence group(Z=-2.049; P=0.022), (Z=-2.310; P=0.010), and the osseous metastasis group was higher than that of the chest wall recurrence group(Z=-1.776; P=0.047) when we compared every two groups.4 We divided the 38 patients with detailed pathological informations into 3 groups according to the primary pathology types: 27 with infilt-rating ductal carcinoma, 5 with infiltrating lobular carcinoma and 6 with other types. The median concentration of the urine CD105 was 40.57pg/ml(14.49~ 411.79pg/ml), 65.00pg/ml(18.00~97.08pg/ml) and 42.43pg/ml(19.66~82.90pg/ml) respectively. There was no statistical difference am-ong the three groups (X~2=0.169; P=0.919).5 We divided the 34 patients with detailed pathological informations into two groups according to the expression of ER, PR and HER-2 status. We definded (-) as negative and (+~+++) as positive. There was 16 ER positive subjects with the median concentration of 40.45pg/ml(15.75~185.43pg/ml), and 18 ER negative subjects with the median concentration of 38.48pg/ml(14.49~411.79pg/ml). There was no statistical difference between the two groups(Z=-0.099; P=0.921). There was 15 PR positive subjects with the median concentration of 40.57pg/ml(15.75~411.79pg/ml), and 19 PR negative subjects with the median concentration of 32.42pg/ml(14.49~ 265.98pg/ml). There was no statistical difference between the two groups(Z=-0.225; P=0.822). There was 27 HER-2 positive subjects with the median concentration of 32.17pg/ml(14.49~265.98pg/ml), and 7 HER-2 negative subjects with the median concentration of 65.00pg/ml(22.35~411.79pg/ml). There was no statistical difference between the two groups(Z=-1.597; P=0.110).Conclusions:1 In breast cancer, the levels of urine CD105 in patients with recurrence or metastasis are higher than that of the patients with no recurrence or metastasis and the health subjects, which indicates that urine CD105 can be used for monitoring the postoperative recurrence or metastasis in breast cancer.2 The level of urine CD105 has no advantage on monitoring the postoperative recurrence or metastasis of breast cancer when it is compared with serum CEA and CA15-3. But the joint positive rate of the three indicators is much higher than the urine CD105, serum CEA and serum CA15-3 positive rate when they are detected separately.3 In breast caner, the level of urine CD105 increases differently when the recurrent or metastatic sites is different. The urine CD105 level in the group of ipsilateral regional lymph nodes metastasis is much higher than that of the groups of visceral metastasis and chest wall recurrence. The level of urine CD105 in the group of osseous metastasis is much higher that of the group of visceral metastasis. There is no statistical difference between the other groups. 4 There is no statistical correlationship between the expression of urine CD105 and the primary pathology types, the expression of ER, PR and HER-2 status.