Study Of The Relevance Between Bone Morphogenetic Protein-4and Breast Cancer Clinicopathological Factors And Bone Metastases

Objective:1.We determined expression of bone morphogenetic protein4(BMP-4) in malignant breast lesions and adjacent normal breast tissues, toexplore its differential expression in breast cancer tissue and normal breasttissue.2.Through analysing the correlation of the expression level of BMP-4withbreast cancer bone metastases and clinical and pathological data, weexplored the relevant factors for predicting breast cancer bone metastases.3. using multivariate unconditional logistic stepwise regression analysis ofbone metastases in breast cancerrisk factors, We established the breastcancer bone metastasis prediction model.Method: Collection pathological specimens of breast cancer patients withsurgical operating in Sichuan Province Mianyang Central Hospital fromJanuary2003to December2008, including paraffin-embedded specimens of228patients with breast cancer,40cases of adjacent2cm normal tissuespecimens used as a control. Immunohistochemical streptavidin-biotin-peroxidase method (SP) was used to detect the expression of BMP-4protein in the cancer tissue and adjacent normal tissue.Through a comprehensive analysis of the228cases of breast cancer patients withclinical and pathological data,we explored the relationship between BMP-4and breast cancer bone metastases and clinicopathological parametersinformation, including age, tumor size, clinical stage, histological grade,ipsilateral axillary lymph node status, estrogen receptor (ER), humanepidermal growth factor receptor2(HER-2), progesterone receptor (PR),tumor suppressor genes (p53), cell proliferation associated nuclear antigen(Ki-67)、E-cadherin. SPSS19.0of Chinese version statistical analysissoftware for data analysis, single factor analysis, respectively, using thechi-square test, Fisher’s precise inspection; group level data using line×list of the chi-square test; bivariate correlation analysis of the use ofspearman method; completion of the use of Logistic regression model inmultivariate analysis, P <0.05was considered statistically significance.Results:1.BMP-4in bone metastasis breast cancer tissue, without bonemetastasis breast cancer tissues and normal tissues positive expression ratewas11.90%(5/42),39.78%(74/186),45.00%(18/40). BMP-4expressionrate in bone metastases breast cancer tissue than those without bonemetastases in breast cancer tissue and adjacent normal tissue wassignificantly lower, the difference was statistically significant (P <0.05).2. BMP-4expression in breast cancer has negative relevance withhistological grade (P <0.05). The expression gradually decreased with histological grade increased (P <0.05). The relevances between BMP-4expression and clinical stage, axillary lymph node status, age, tumor size,menopausal conditions, PR, HER-2, ER, p53, E-cadherin and Ki-67wereno statistically significant (P>0.05).3breast cancer bone metastasis-related risk factors for univariate analysis:The relevances between breast cancer bone metastasis and age, tumor size,menopausal conditions, PR, p53, E-cadherin and Ki-67were no significantcorrelation (P>0.05). The relevances between BMP-4expression status andaxillary lymph node status, clinical stage, histological grade, HER-2and ERexpression were statistically significant (P <0.05).4.Clinical stage, Histological grade, Axillary lymph node metastasis、BMP-4、HER-2and ER brought into the logistic regression analysis,establishing the breast cancer bone metastsis-prediction model, Glikelihood ratio test was statistically significant (P <0.05). The discriminantaccuracies of no occuring bone metastases and bone metastases in five yearswere73.1%and71.4%, the average accuracy rate of72.5%.Conclusion:1. BMP-4expression in breast cancer tissue has a negativerelevance with histological grade, which showed that the breast cancer cellshad lower level or absence expression of BMP-4were of lower degree ofdifferentiation, the higher degree of malignancy.2. BMP-4expression has a negative relevance with breast cancer bone metastasis, Patients with BMP-4positive expression have low probabilityof bone metastasis occurrence,and later in the transfer time than those ofBMP-4negative expression, BMP-4is a breast cancer bone metastasis non-risk factor。3.Clinical stage Ⅲ, Histological grade Ⅲ， HER-2positive expressionwere the main risk factors for breast cancer bone metastasis, BMP-4positive expression is the protective factors for breast cancer bonemetastasis.establishing a logistic regression model, likelihood ratio G-testwas statistically significant, the fit is good.It can be uesed to predict breastcancer bone metastasis.