P65 And β-catenin Expression: The Role In Carcinogenesis And Development Of Human Breast Cancer

[Background and Objective] Breast cancer is one of the most common malignant tumors in women with 75% of which exhibiting invasive ductal carcinoma (IDC) when diagnosed. It was demonstrated that ductal and lobular proliferations of breast lesions were statistically associated with increased risk of subsequent breast cancer. Women with biopsy-demonstrated proliferative diseases without atypia were reported to have a 1.5-2-fold increase in breast cancer risk, however those with atypical hyperplasia having a 4-5-fold elevation compared with women of similar age. Even though the exact molecular mechanism and pathologic sequence of breast carcinogenesis have not yet been clear till now, it is widely accepted that many of the molecular events that control normal development of the mammary gland are the same events that, when misregulate, result in cancer. P65, a key protein of NF-kB signal transduction pathway and β-catenin, a key component of Wnt , both keeping the critical role in cell survival, adhesion and proliferation, were proved not only to implicate in breast carcinogenesis in animal model and had also been found abnormal activation in many types of cancers including breast cancer. In this study, immunohistochemical staining was used attempting to determine P65 and β-catenin expressions and their relationship in human mammary carcinogenesis and development, besides, correlation of gene expressions with clinicopathological parameters was also analyzed. [Materials and Methods] One hundred and sixty-five breast's specimens were obtained either by biopsy or surgical operation. Among them, there were cases with intraductal papilloma n=25, DBCH (disease of the breast cystichyperplasia) n=27, DBCH with ADH(atypical ductal hyperplasia)n=26, DCIS(ductal carcnoma in situ)n=29 and IDC ( invasive ductal cancinoma ) n=58. Immunohistochemical staining were used to examine the expression of P65 and (3-catenin. P65 and (3-catenin expressions and theirrelationship with related clinicopathological factors were analyzed in the breast diseases All the data were statistically managed with SPSS 10.0 for windows. [Results] Our study revealed: l.The positive rates of P65 expression in intraductal papilloma, DBCH, DBCH with ADH, DCIS, and IDC were 8.0%, 11.1% ,42.3% ,31.0% and 48.3%, respectively.The rates in DBCH with ADH, DCIS, IDC were higher than those in intraductal papilloma and DBCH (P<0.05). 2. P65 expression was significantly correlated with lower tumor grading, maxilary lymph node metastasis, and later TNM staging (P<0.05), but not with tumor size and age of the patient.3. The positive rates of (3-catenin expression in intraductal papilloma, DBCH, DBCH with ADH, DCIS, and IDC were 4.0%, 3.7% , 23.1% , 72.4% and 79.3 %, respectively. The rates in DBCH with ADH elevated significantly higher than those in intraductal papilloma and DBCH(P<0.05), and the rates in DCIS and IDC were higher than that in DBCH with ADH too. (P<0.05) 4. The expression of simple membranous P-catenin was statistically related with tumor size, lymph node metastasis and TNM staging (P<0.05), the expression rate was higher in patients with smaller size, no lymph node metastasis and stage I or II, but not with tumor grading and age of the patientThe co-expression of membranous and cytoplasmic P-catenin was significantly correlated with lymph node metastasis, the rate rised higherly only in patients with lymph node metastasis (P<0.05). Furthermore, the possibility of lymph node metastasis was higher in membranous and cytoplasmic P-catenin co-expression group than in membranous group.5. Lymph node metastasis, later TNM stage( III) and lower grade( III) were founded higherly in tumors with positive expressions of P65 and P-catenin.There was no clear relationship between P65 and P-catenin expression in intraductal papilloma and DBCH, but positive correlation among DBCH with ADH, DCIS, and IDC.[Conclusion] 1. Positive expression of P65 and P-catenin occurred early and continued to exist during neoplastic transformation of mammary cells;2. P65 expression was significantly correlated with lower tumor grading, maxilary lymph node metastasis, and later TNM staging (P<0.05), the co-expression of membranous and cytoplasmic P-catenin was significantly related with lymph node metastasis, which implied they might be risk factors of poor prognosis, whereas the expression of membranous p-catenin only was negtively correlated with tumor size, lymph node metastasis, and TNM staging , it might be a protective factor of good prognosis.3.There was no relationship between P65 and p-catenin expression in inttaductal papilloma and DBCH, while positive correlation among DBCH with ADH, DCIS, and IDC.