Abstract

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.

Highlights

  • (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both ductal carcinoma in situ (DCIS) and invasive mammary carcinoma

  • In this study of 149 cases of primary symptomatic breast carcinoma taken from the Nottingham/Tenovus Primary Breast Carcinoma Series (146 invasive carcinomas and three cases of DCIS) we have demonstrated a statistically significant association between expression of the p53 protein and high tumour grade, expression of epidermal growth factor receptor (EGFR), and c-erbB-2 protein overexpression

  • Other groups have found a similar association of p53 protein expression in breast carcinoma and high tumour grade (Cattoretti et al, 1988a; Ostrowski et al, 1991; Walker et al, 1991) with a similar trend towards poorer survival in patients with tumours expressing the p53 protein noted in one other published series (Ostrowski et al, 1991)

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Summary

Materials and methods

Antibodies pAbl801 is a mouse monoclonal anti-p53 antibody (EuroPath Ltd, Bude, Cornwall, UK) which recognises an epitope near the N-terminus of both the wild and mutant forms of the human p53 protein (Banks et al, 1986). EGFR-1, a mouse monoclonal anti-epidermal growth factor receptor antibody (Amersham Ltd, Amersham, UK) was utilised to examine expression of EGFR. Examination of overexpression of the c-erbB-2 protein was performed using the polyclonal rabbit antibody 21N (Venter et al, 1987), a generous gift of Dr W.J. Gullick, ICRF Molecular Oncology Group, London. At least 500 carcinoma cell nuclei were counted in each of six areas of the tumour for assessment of p53 immunoreactivity. Homogenous or heterogeneous tumour membrane immunoreactivity was utilised to indicate tumour EGFR expression. Positive tumour cell membrane immunoreactivity with EGFR-1 had been previously shown to indicate EGFR expression in a number of control tumours which showed high level expression of EGFR using an EGFR radioimmunoassay. Either homogenous or heterogeneous was utilised as the sole criterion of c-erbB-2 oncoprotein overexpression

Statistical analysis
Patients and tissues
Results
Other types
Clinicopathological associations
Clinicopathological associations and patient survival
Oestrogen receptor pos Oestrogen receptor neg
Findings
Discussion

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