Expression of bax and p53 Proteins in the Tumorigenesis and Progression of Breast Carcinomas

Abstract

Objectives: Dysregulation of normal programmed cell death mechanisms plays an important role in the pathogenesis of breast cancer. The purpose of this study was to investigate the role of bax and p53 expression in tumorigenesis and progression of breast carcinoma as well as their relationship with proliferative and apoptotic activity. Methods: We used immunohistochemical methods and in situ detection of apoptotic cells to examine 30 carcinomas in situ (CIS), 131 invasive breast carcinomas and 45 lymph node metastases. Results: In 25% (33 of 131) of invasive breast carcinomas examined, bax expression was absent, while p53 accumulation was present in 37% (49 of 131). Interestingly, p53 accumulation and loss of bax expression occur in breast CIS as frequently as in invasive breast carcinoma. Thus, in 17% (5 of 30) of CIS bax expression was absent, and 30% (9 of 30) presented nuclear expression of p53. p53 accumulation was related to apoptosis and proliferative activity. However, the protein level of bax was unrelated to all parameters studied, including proliferation and apoptosis of tumor cells. A multivariate analysis of disease-free survival demonstrated that p53 accumulation and bax expression are not significant independent indicators of prognosis in operable breast carcinoma. Our results also show that the proportion of bax- and p53-positive cells does not vary between primary and metastatic tumors. Conclusions: p53 accumulation and loss of bax expression influence the acquisition of a malignant phenotype but seem to have no further impact on tumor progression.

Reduced mRNA and protein expression of BCL-2 versus decreased mRNA and increased protein expression of BAX in breast cancer brain metastases: a real-time PCR and immunohistochemical evaluation

“…On the one hand, BAX overexpression has been associated with tumor size and tumor stage in a series of 121 patients 25 . On the other hand, loss of BAX seems to be as frequent in carcinoma in situ and invasive breast cancer indicating loss of BAX as an early event in breast cancer genesis 26 . Remarkably, in breast tumor cells BAX plays an essential role in the pro-apoptotic effect of maspin, which can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro 27 .…”

Expression of apoptosis‐related protein Bcl‐2 correlates with breast carcinomas of luminal or basal‐like subtype

“…Positive immunostaining for Bcl‐2 and Bax is noted in 15–82.8% and 50–75% of breast cancers, respectively 31–34 . In breast carcinomas, Bax expression is associated with positive lymph node status, age, tumor size and disease stage 32,34 .…”

“…30 Positive immunostaining for Bcl-2 and Bax is noted in 15-82.8% and 50-75% of breast cancers, respectively. [31][32][33][34] In breast carcinomas, Bax expression is associated with positive lymph node status, age, tumor size and disease stage. 32,34 Expression of bcl-2 is associated with hormone receptor expression, small tumor size and low nuclear grade.…”

ERα and ERβ expression in correlation with Ki-67, Bcl-2 and Bak in primary tumors and lymph node metastases of breast cancer: The effect of pre-operative chemotherapy

“…The range of factors that stimulate and inhibit the processes of proliferation and apoptosis determine survival chances of neoplastic cells in primary tumor and metastatic foci (13,14). However, despite intensive studies regarding ER expression and markers of proliferation and apoptosis in primary breast cancer, relatively little is known about the expression of these markers in metastatic foci, the main target of antineoplastic therapy.…”