Epidermal growth factor receptor in human breast cancer: Correlation with cytosolic and nuclear ER receptors and with biological and histological tumor characteristics

doi:10.1016/0277-5379(90)90223-G

European Journal of Cancer and Clinical Oncology

Volume 26, Issue 3, March 1990, Pages 283-290

European Journal of ...

https://doi.org/10.1016/0277-5379(90)90223-G Get rights and content

Abstract

Epidermal growth factor receptor (EGFr) and cytosolic (cER) and nuclear (nER) estradiol receptors were quantified in 220 primary breast cancers. The EGFr was significantly more frequent (χ² = 5.9; P < 0.025) and its concentration was significantly higher (P < 0.001) among ER− tumors than in ER+ tumors. There was a significantly greater proportion (χ² = 6.4; P < 0.05) of node involvement in EGFr+/ER+ tumors than in EFGr−/ER+. Increases in the proportion of EGFr+ in ER− tumors are parallel to Scarff-Bloom scores (χ² = 6.1; P < 0.05) and there is a significant trend (Spearman r_s = 0.25; P < 0.05) towards increased EGFr concentrations with histologic dedifferentiation.

In ER+ tumors the median concentrations of EGFr in the different age groups show a linear correlation (LCC = 0.89; P < 0.05) and follow a parallel profile with the medians of nER. These findings support the hypothesis that EGFr is a bad prognosis factor and suggest that EGFr expression and concentration in ER+ tumors might be considered an estrogenic action mediated through the binding of ER to their nuclear acceptors.

References (24)

JRC Sainsbury et al.
Epidermal growth factor receptors an estrogen receptors in human breast cancer
Lancet
(1985)
F Battaglia et al.
Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement
Eur J Cancer Clin Oncol
(1988)
MM Bradford
A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principle of protein-dye binding
Anal Biochem
(1976)
R James et al.
Polypeptide growth factors
Ann Rev Biochem
(1979)
P Bolufer
Factor de crecimiento epidérmico y su papel en el desarrollo tumoral
Oncología
(1988)
CR King et al.
Amplification of novel v-erb B related mammary carcinoma
Science
(1985)
AL Schechter et al.
The neu gene: an erbB-homologous gene distinct from and unliked to gene encoding EGF receptor
Science
(1985)
F Battaglia et al.
Receptors for epidermal growth factor and steroid hormones in human breast cancer
Oncology
(1988)
JC Delarue et al.
Epidermal growth factor receptor in human breast cancers: correlation with estrogen and progesterone receptors
Breast Cancer Res Treat
(1988)
E Spitzer et al.
EGF binding is quantitatively related to growth in node-positive breast cancer
Breast Cancer Res Treat
(1988)

JRC Sainsbury et al.

Presence of epidermal growth factor receptor as indicator of poor prognosis in patients with breast cancer

J Clin Pathol

(1985)

S Nicholson et al.

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients

Br J Cancer

(1988)

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This chapter describes the growth factor signal transduction and hormone independence in breast cancer. Mitogenesis in breast tissue is mediated in part through the interaction of the steroid hormone estrogen, denoted E2 or 17-β-estradiol, with an intracellular protein, the estrogen receptor (ER). The E2–ER complex acts as a transcription factor to induce expression of specific genes. Hormone-dependent breast cancers express ER and are stimulated by E2, which acts in these cells in part through induction of genes coding for polypeptide growth factors that in turn promote cell growth. The E2-mediated growth stimulation of these cells leads to the use of antiestrogenic drugs to inhibit the growth of these tumors. Hormone-independent breast cancers are not stimulated by E2 and may have no detectable ER expression and are therefore insensitive to antiestrogen treatment. These tumors often express growth factors at high levels. This inverse correlation between ER and over expression of growth factors suggests that the expression of such proteins in an unregulated manner by hormone-dependent breast cancer may contribute to its growth in the absence of E2. It leads to the hypothesis that the constitutive expression of growth factors by a hormone-dependent cancer may contribute to the development of hormone independence.
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The aim of this study is to evaluate the prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) expression in primary breast cancer (BC) and their prognostic implications when combined with estradiol receptor (ER) status. In this work, 825 BCs were studied. Neu amplification was evaluated by dot-blot and EGFR expression was evaluated by ligand binding assay using I¹²⁵-EGF. Neu, EGFR, estradiol and progesterone receptors (ER and PR) had a marked influence on disease free survival (DFS) in univariate analysis. In node-negative (NO) cases only neu was associated with short DFS (p = 0.005). However, in node-positive (N + ) cases both EGFR (p = 0.005) and neu (p = 0.002) influenced DFS. None of the biological markers were significant predictors for overall survival (OS) in NO/BC.. On the contrary, in N + /BC, EGFR + (p = 0.003) was associated with short OS. The EGFR + /neu + phenotype represented a sub-group with an even worse prognosis with respect to DFS (p = 0.0034) as well as EGFR + /ER - tumors (p = 0.005). Moreover, neu + /ER - patients also had a high probability of relapse (p = 0.0000) and death (p = 0.006). C-erbB-2/neu, EGFR, histological grade, pN, pT and ER were subjected to a Cox multivariate regression analysis: neu was the most important parameter in predicting recurrence, and EGFR was a significant predictor for OS.
Specific oncological contribution of cathepsin D and pS2 in human breast cancer: Their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification
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The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
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Amplifications of neu and c-myc were evaluated in 218 and 145 breast cancers (BC), respectively. Oncogene amplifications were determined for the most part by Southern blot. An association between the proportion of nodes affected and the intensity of neu amplification in estadiol receptor negative (ER-) BC was found (P = 0.028), which was confirmed by the multi-factor analysis of variance (P = 0.05). A significantly greater incidence in neu amplifications among BC with metastases was also found (P = 0.031). A strong association (P = 0.01) between the neu and myc amplification was observed. There is a strong association between myc amplification and ER- BC (P < 0.01). It is concluded that (1) the combination ER- with neu amplification might define a new group of more aggressive BC, as is suggested by their associated nodal involvement; (2) the linkage of myc amplifications with ER- BC and high grade of neu amplification might reflect a trait of tumor aggressivity.

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^☆: This study was supported by the Spanish FIS grant 88/1832.

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Epidermal growth factor receptor in human breast cancer: Correlation with cytosolic and nuclear ER receptors and with biological and histological tumor characteristics☆

Abstract

Lancet

Eur J Cancer Clin Oncol

Anal Biochem

Polypeptide growth factors

Ann Rev Biochem

Factor de crecimiento epidérmico y su papel en el desarrollo tumoral

Oncología

Amplification of novel v-erb B related mammary carcinoma

Science

The neu gene: an erbB-homologous gene distinct from and unliked to gene encoding EGF receptor

Science

Receptors for epidermal growth factor and steroid hormones in human breast cancer

Oncology

Epidermal growth factor receptor in human breast cancers: correlation with estrogen and progesterone receptors

Breast Cancer Res Treat

EGF binding is quantitatively related to growth in node-positive breast cancer

Breast Cancer Res Treat

Presence of epidermal growth factor receptor as indicator of poor prognosis in patients with breast cancer

J Clin Pathol

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients

Br J Cancer