The Study Of The Expression Of TGF-β₁ And T_βRâ…¡ In Breast Cancer And Their Clinical Significance

Backgrounds and Objectives:Transforming growth factor-beta (TGF-β) is a pleiotropic growth factor that plays a critical role in the development of embryo, modulating cell growth and differentiation, the balance of extracellular matrix and tumorigenesis and invasiveness. Generally believed, there are three isotypes of TGF-β in mammalian animals: TGF-β1, TGF-β2and TGF-β3. Among them TGF-β1 is the most potent physiological inhibitor of normal breast epithelial cells, and loss of responsivess to its effects has been associated with malignant transformation and tumorigenesis. Relatively, there are three kinds of its receptor: TβR I , TβRIIand TβRIII. Evidence suggests that loss of expression of TβR II is the critical cause of tumorigenesis and the anti- TGF-β in tumor cells. Especially it is remarkable that the responsivess of breast cells to TGF-β has experienced a so-called "paradoxical switch" in the course of the development of breast tissue from normal to hyperplasia, DCIS and invasive cancer.Regarded DCIS as the boundary, before it TGF-β functions as a growth inhibitor, but after it TGF-P turns into promoting tumor progression. The specialty of TGF-P in the progression of breast cancer makes us recognized that the current clinical application of tamoxifen and ionizing radiation to treat breast cancer may exist certain mistake area, because the last two methods can ascend the level of TGF-β in some degree. In another hand, the ever-increasing number of clinical DCIS cause us to think that it must be encouraging if we can put TGF-P into the use of breast surgery so as to direct clinical treatment of DCIS. According to these actualities and assumptions, we researched the expression of TGF-β and TβRII in normal breast tissue, DCIS and invasive breast cancer by the use of immunohistochemistry technique.Material and Methods:Immunohistochemical streptavidin/peroxidase technique was used to detect the expression of TGF-β1 and TpBII in archival breast samples including 50 cases of invasive mammary carcinoma (IMC), 12 cases of ductal carcinoma in situ(DCIS) and 15 cases of normal breast tissue. Among 50 cases of breast cancer tissue, there are 5 cases of medullary carcinoma, 4 cases of mucous carcinoma and 41 cases of invasive ductal carcinoma. Furthermore, statistics analysis for SPSS10. 0 was used to investigate the relationships between TGF-P signal pathway and the features of clinical pathology of breast cancer.Results:1. The expression of TGF-β1 : (1) There were 31 positive cases in 50 samples of IMC, and the positive rate was 62%. In comparison with normal breast tissue the difference was significant (P=0.016). However there were no significant correlations (P >0. 05) between DCIS and normal breast tissue. But if DCIS was combined with IMC,2. the difference between them and normal breast tissue would showsignificant (P=0. 029). (2) The positive expression of TGF-β1 among the different age groups or different histological grades showed no significance (P>0. 05); But in breast cancer the " II ~IIIstage" showed significantly higher(P=0. 026) than "0 ~I stage" . (3) There were 22 positive cases in 30 cases of the group with axillary lymph node metastasis, and its positive rate was up to 73.33%, which was significantly higher(p=O. 018) than the opposite group.3. The expression of TβRII: (1) There were 11 positive cases among 15 cases of normal breast tissue, and the positive rate was 73. 33%. While there were 6 positive cases in 12 samples of DCIS, and 20 positive cases in 50 cases of IMC. But the difference among them was not significant(P =0. 065). (2) The positive expression of TβRII among different age groups or different TNM stages showed no significance (P >0. 05); But in breast cancer the difference among the different histology groups showed significant (P=0.0013). (3) The difference between the group with axillary lymph node metastasis and the opposite group was not significant (P=0.065).4. The correlation between the positive expression of TGF-β1 and TβRII...