p53 and c-erbB-2 Protein Expression in Breast Carcinomas: An Immunohistochemical Study Including Correlations with Receptor Status, Proliferation Markers, and Clinical Stage in Human Breast Cancer

Abstract

Receptor status, proliferative activity, loss of differentiation, inactivation of tumor suppressor genes, and overexpression of oncogenes are related events that may affect the prognosis of patients with breast cancer. Ninety-seven unselected breast carcinomas were immunostained for estrogen and progesterone receptors, Ki-67 proliferation-associated antigen, p53 tumor suppressor gene product (p53), and c-erbB-2 protein. Immunohistochemical results and clinical data were compared. Altered p53 expression (regarded as indirect indication of inactivating gene alterations) was found in 25.8% of cases and was associated with a high Ki-67 labeling index, high mitotic count, and high histologic grade, with c-erbB-2 overexpression, and with negative estrogen and progesterone receptor status. p53 immunostaining could be found also in cytologic samples and correlated with p53 immunoreactivity on frozen sections of the corresponding tumors. c-erbB-2 protein overexpression was seen in 24.7% of cases and was associated with p53 altered expression and negative receptor status. Double immunohistochemical staining showed p53 and c-erbB-2 immunoreactivity in the same cells. Median and mean +/- standard deviation Ki-67 labeling index values were 15 and 16.32 +/- 10.05, respectively. Ki-67 labeling index was correlated with high mitotic count and was positively associated with histologic grade, negative progesterone receptor status, and p53 expression. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with grading. The direct relation of p53 protein alterations with c-erbB-2 overexpression may be interpreted in light of the multistep model of tumor progression. Cases with altered expression of both p53 and c-erbB-2 proteins could be interpreted as having lost one inhibitory control mechanism of cell proliferation and having gained one activator of the malignant potential. However, in comparing cases with the p53 + c-erbB-2 + phenotype with cases showing positivity for only one of these gene products, no association with higher stages was seen. Detection of p53 altered expression on cytologic samples of malignant tumors may have diagnostic relevance, and p53 immunostaining may prove to be an additional diagnostic criterion in cytologic diagnosis.

p53 protein as a prognostic indicator in breast carcinoma: a comparison of four antibodies for immunohistochemistry

“…These results are in keeping with the findings of previous similar studies (Cattoretti et Previous studies have shown that the presence of detectable p53 protein in breast cancer is significantly correlated with increased levels of c-erbB-2 oncoprotein (Iwaya et al, 1991;Barbareschi et al, 1992;Poller et al, 1992;Spandidos et al, 1992;Martinazzi et al, 1993), and EGFR Poller et al, 1992), but similar correlations were not observed in our material. Correlation between Rb and p53 structural abnormalities has been reported in breast carcinoma and in several other malignant tumours (Hall and Lane, 1994).…”

ErbB2 overexpression in p53‐inactivated mammary epithelial cells

“…In the immunostaining analyses using clinical breast cancer tissues, ErbB2 protein overexpression was frequently found with p53 altered expression [32,33]. In addition, double immunohistochemical staining results showed p53 and ErbB2 immunoreactivity in the same cells [33]. Hence, it would be plausible to hypothesize that p53 function regulates the expression of ErbB2.…”

Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers

“…Diaminobenzidine was used as the peroxidase substrate and the sections were counterstained with methylgreen. Only cases exhibiting distinct membrane staining in more than 80% of Paget's cells were identified as positive for c-erbB-2 overexpression (Barbareschi et al, 1992).…”