| Background: Breast cancer, which is the second leading cause of cancer death in women, metastasizes to skeletal in greater than 80% of patients with advanced disease. Skeletal metastases, which invariably lead to hypercalcemia, bone pain, fractures and nerve compression, cause increased morbidity and mortality in patients with cancer. A number of studies have suggested that the frequency of bone metastasis of breast cancer (87%) was much higher than those of lung (27%) and liver (27%) cancer, demonstrating that bone is the most common site of the first distant relapse in breast cancer. Between the breast cancer cell and the bone cell has the close reciprocity, which has involved a lot of cell factors, growth factors and signal channels. Parathyroid hormone-related protein (PTH-rP) was isolated from human lung cancer, breast cancer and renal cell carcinoma as a hypercalcemic factor, and played a role in breast cancer metastasis to skeletal.Objective: This study was to examine the expression of PTH-rP in breast cancer with skeletal metastases and investigate the relationship between PTH-rP and development and in breast cancer with skeletal metastases.Methods: We retrospectively analyzed 35 patients who had all undergone a mastectomy and developed skeletal metastases and 100 breast cancer postoperative patients who without developing any distant metastasis which were randomly selected to observe the differences between the two teams in clinical and pathology. immunohistochemical staining method was used to detect the protein expression of PTH-rP in 35 patients who had all undergone a mastectomy and developed skeletal metastases and 35 breast cancer postoperative patients who without developing any distant metastasis which were randomly selected. All eases were collected in the first affiliated hospital of Dalian medical university from 1998 to 2005. Patients were followed up for at the end of experiment or until death. Results: Comparing the clinical data of breast cancer patients who developed skeletal metastases and patients without skeletal metastases show: There were significant differences between 2 groups in tumor size, clinical stage,lymph node status and estrogen receptor (ER) status (P<0.05). There were not significant difference in age (P=0.294), histological type (P=0.673), Menopausal status (P=0.273), progesterone receptor(PR) status (P=0.077) and HER-2 status (P=0.898). Immunohistochemical analysis showed that 28 had tumors positive for PTH-rP in 35 patients who developed skeletal metastases. There were 13 had tumors negative for PTH-rP in 35 patients without developed skeletal metastases. The expression status of PTH-rP was significantly difference between 2 groups patients (P<0.05). Survival analysis showed that the breast cancer patients who had tumors positive for PTH-rP survival rate was significantly lower than in patients who negative (P<0.05). In breast cancer patients who developed skeletal metastases,the expression status of PTH-rP was related with ER status and HER-2 status (P<0.05), while not related with age (P=1.000), tumor size (P=0.723), histological type (P=0.670),clinical stage (P=1.000), lymph node status (P=0.426), Menopausal status (P=0.691), and PR status (P=0.104). Multivariate analysis showed that tumor size,clinical stage, lymph node status, ER status and Expression of PTH-rP status was independent factors in breast cancer patients who developed skeletal metastases (P<0.05),while age (P=0.315),histological type (P=0.054),Menopausal status (P=0.421),PR status (P=0.841) and HER-2 status (P=0.351) are not independent factors.Conclusions:1. PTH-rP play a role in development and progression of breast cancer with skeletal metastases.2. Tumor size, clinical stage, lymph node status, estrogen receptor, and PTH-rP expression constitutes risk factors for breast cancer with skeletal metastasis. |
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