Relationship Between BRCA1 Expression And ERK Signal Transduction Pathway In Familial Breast Cancer

ObjectiveBreast cancer is one of the most common tumors affecting women. Breast tumors of patients with germ-line mutations in the BRCA1 and BRCA2 genes have more genetic defects than sporadic breast tumors.The signal transduction pathway of the mitogen-activated protein kinase (MAPK) plays a critical role in cell proliferation, survivorship, differentiation. MAPK signal transduction pathway played an important role in BRCA-associated breast cancer.In this study, I use immunohistochemistry method to detect the expression of BRCA1 and ERK/MAPK in breast cancer to find if the expression of BRCA1 in familial breast cancer is higher than sporadic ones and if it makes its effect through ERK/MAPK signal transduction pathway.Materials and methodsSpecimen84 cases of breast cancer embedded in paraffin were obtained from the Tumor Surgery of the First Affiliated Hospital of China Medical University from 1998 to 2006.AgentsBRCA1 monoclonal antibody, S-P staining kit and DAB Developer were obtained from Fuzhou Maixin Biotechnology Company. ERK1/2,pERK1/2 antibody were supported by Wuhan Boster Biotechnology Company. MethodI detect BRCA1,ERK1/2 and pERK1/2 by the method of IHC.Judgment criterionBRCA1: Judging by the quantity of cancer cell staining: negative(-): positive cell<5%; light positive(+): positive cell 5～20%; meddle positive (++): positive cell 21～50%; strong positive(+++):positive cell>80%.ERK1/2: Judging by the quantity of cancer cell staining: negative(-): positive cell<30%; light positive(+): positive cell 30～60%; strong positive(++):positive cell>60%.pERK1/2: positive(+): cell nuclear is brown stained; negative(-): cell nuclear is not stained.Statistics analysisI use x~2 test to analyse.Results1. Significant difference of BRCA1 expression was found between the group of familial breast cancer(69.0%, 29/42) and that of sporadic breast cancer(9.52%, 4/42).2. Significant difference of ERK1/2 expression was found between the group of familial breast cancer(66.7%, 28/42) and that of sporadic breast cancer(33.3%, 14/42). There was also significant difference of pERK1/2 expression between the group of familial breast cancer(64.3%, 27/42) and that of sporadic breast cancer(28.6%, 12/42).3. Significant difference of ERK1/2 expression was found between the group of positive BRCA1 expressions(69.7%, 23/33) and that of negative BRCA1 expressions(37.3%, 19/51). There was also significant difference of pERK1/2 expression between the group of positive BRCA1 expressions (66.7%, 22/33) and that of negative BRCA1 expressions (33.3%, 17/51).Conclusion1. Expression of BRCA1 in familial breast cancer is higher than that in sporadic breast cancer. It means BRCA1 playing a very important role in the familial breast cancer.2. Expressions of ERK1/2 and pERK1/2 in familial breast cancer are higher than those in sporadic breast cancer. It means ERK/MAPK signal transduction pathway is abnormal activated. It may play a very important role in the develop of familial breast cancer.3. Expressions of ERK1/2 and pERK1/2 in positive expression of BRCA1 protein are higher than those in negative ones. It means BRCA1 may make its effect through ERK/MAPK signal transduction pathway.