Proliferative activity in breast carcinoma evaluated bv BrdU and PCNA: Correlation with expression of p53, c-erbB-2, estrogen receptor and P-Glycoprotein

Abstract

The proliferative activity in 35 cases of breast carcinoma was evaluated by bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) and was compared with benign breast lesion. Overexpression of p53 and c-erbB-2 oncoprotein, presence of estrogen receptor (ER) and cellular localization of multidrug resistance gene product P-glycoprotein (P-gp) were immunohistochemically examined to investigate the relation with the proliferative activity and clinicopathologic characteristics. The mean BrdU labeling index (LI) was 12.6% and PCNA labeling rate (LR) was 33.5% in breast carcinomas, and good correlation was found between them. The proliferative activity of breast carcinomas was significantly higher than that of benign lesions. The BrdU LI correlated positively with tumor size, histologic grade, TNM stage and p53 immunoreactivity, and negatively with the presence of ER. PCNA LR correlated with histologic grade and expression of p53. p53 protein was demonstrated in 43% of the breast carcinomas and correlated with proliferative activity. The extent of p53 immunoreactivity on carcinoma cells was also related to BrdU LI. c-erbB-2 oncoprotein was demonstrated in 51% of the breast carcinomas and correlated with histologic grade. ER was found in 34% of the breast carcinomas and correlated negatively with histologic grade, lymph node metastasis and TNM stage. P-gp was observed in 49% of the breast carcinomas and no correlation was found with clinicopathologic characteristics. None of the benign lesions expressed p53 protein, c-erbB-2 oncoprotein and P-gp. BrdU is a reliable standard and a more useful tool for the evaluation of proliferative activity of breast tumors. High proliferative activity, overexpression of p53 protein and the absence of ER are considered as a high grade malignancy of breast carcinoma. Expression of c-erbB-2 oncoprotein and P-gp may be related to malignant transformation of breast tumors.