Immunohistochemical Status of p53, MDM2, bcl2, bax, and ER in Invasive Ductal Breast Carcinoma in Tunisian Patients

Abstract

TP53 gene alterations have been associated with sporadic breast cancer. To assess the role of p53 in invasive ductal carcinoma (IDC) of the breast among Tunisian patients, p53 protein status was studied by immuno-histochemical analysis. The p53 protein was expressed in 41 of 70 (58%) tumors. Study of the status of its target gene expression showed that MDM2 was overexpressed in 43 tumors (61%), bcl2 in 29 (41%), and bax in only 9 (12%). Estrogen receptor (ER) was detected in 38 tumor tissues (54%). The accumulated p53 was significantly associated with MDM2-positive, bcl2-negative, and ER-negative tumors (P = 0.024, P = 0.000027, and P = 0.000008, respectively), whereas with bax the correlaton was not significant. Bcl2 immunostaining displayed a positive correlation with ER (P = 0.001). A significantly higher fraction of p53-positive cells was observed in ER-negative SBRII-SBRIII tumors than in ER-positive SBRI-SBRII tumors (P = 0.000066). bcl2-positive tumors were significantly correlated with ER-positive/SBRI-SBRII tumors (P = 0.007), but negatively correlated with p53/bax (P = 0000004). MDM2 immunostaining displayed the same phenotype as p53 in the correlation with bcl2 and ER (P = 0.003), strengthened by significant associations between MDM2-positive/p53-positive and bcl2-negative or ER-negative, respectively (P = 0.00005 and P = 0.000001, respectively). MDM2-positive cells were significantly correlated with the p53-positive/bax-negative phenotype (P = 0.04). These results suggest that p53 accumulated in these tumor tissues is associated with bad prognostic markers (ER-negative, SBRIII) of IDC. MDM2 overexpression might be responsible for the accumulated p53 value in IDC. Regulation of the apoptotic process is involved in IDC; bcl2 is associated with a good prognostic marker (ER-positive and SBRI-II), whereas the regulation of bax is complex and does not necessarily correlate with the overexpression of p53.

Bad expression predicts outcome in patients treated with tamoxifen

“…However, Bcl-2 correlated significantly with favourable tumour features such as DNA diploid status and expression of oestrogen and progesterone receptors [34]. This has also been seen in other studies [35]. Our results do not show any link between expression of Bcl-2 and Bcl-xl and apoptosis measured by TUNEL experiment.…”

Association of TP53codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients

“…p53 also positively regulates MDM2 expression, thereby creating a negative feedback loop [3]. Overexpression of MDM2 is observed both in epithelial cells of transgenic mice with induced mammary carcinomas [4] and in multiple human tumors, including breast cancer [5-7]. …”

Immunohistochemical Detection of Mdm2 and p53 in Feline Mammary Gland Tumors

“…Expression of Mdm2 is consequent upon p53 activation. Concomitant overexpression of Mdm2 and p53 has been observed in human epithelial neoplasms including those of the breast [3,4], prostate [16], stomach [13], liver [7], and bladder [29] and associated with high tumor grade and tumor invasiveness and aggressiveness. A reciprocal relationship between the presence of a p53 mutation and Mdm2 gene amplification was demonstrated in canine soft-tissue sarcomas [25].…”

“…This creates a feedback loop that regulates both the activity of p53 protein and the expression of Mdm2 gene [21,30]. Overexpression of p53 protein has been reported in feline mammary gland tumors and squamous cell carcinomas [22], and in human malignant epithelial tumors of the breast [3], stomach [13], kidney [11], and liver [7].…”