Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades

doi:10.1016/0304-3835(93)90062-E

Cancer Letters

Volume 75, Issue 3, 20 December 1993, Pages 195-206

https://doi.org/10.1016/0304-3835(93)90062-E Get rights and content

Abstract

One hundred and nine primary breast cancers were analysed to assess the presence of the HER-2/neu gene product (p185), the oestrogen (ER) and the progesterone (PR) receptors, and the total cathepsin D status. An enzyme-linked immunosorbent assay (ELISA kit, Oncogene Science Inc.) was used for the evaluation of p185 in pellets obtained after a 100 000 × g centrifugation, ER and PR were measured by enzyme immunoassay (EIA kit, Abbott Laboratories), and the total cathepsin D content was evaluated by immunoradiometric assay (IRMA kit, CIS Biointernational). We showed that the ELISA kit is feasible to quantify the p185 present in breast cancer cell membranes, and that the detector antibody recognises a protein of approximately M_r 185 000. The detected antigen was inversely related to both ER and PR, but it did not correlate to total cathepsin D. No significant differences were found in the expression of p185, ER, PR, cathepsin D between infiltrating ductal carcinomas without special features (NOS) and non-ductal (non-NOS) carcinomas. Nevertheless, in NOS carcinomas, a trend was observed in the p185 levels expressed by the tumours with different histological grades, in that p185 concentration was higher in the poorly differentiated grade 3 with respect to grade 2 and grade 1.

References (40)

S. Antoniotti et al.
Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer cells in vitro
Eur. J. Cancer
(1992)
M.W. Beckmann et al.
Detection of the HER-2/neu proto-oncogene protein p185^erbB2 by a novel monoclonal antibody (MAB-145ww) in breast cancer membranes from oestrogen and progesterone receptor assays
Eur. J. Cancer
(1992)
J.P. Brouillet et al.
Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness
Eur. J. Cancer
(1990)
P. Lipponen
Expression of c-erbB-2 oncoprotein in transitional cell bladder cancer
Eur. J. Cancer
(1993)
S. Marsigliante et al.
Transcriptionally active non-ligand binding oestrogen receptors in breast cancer
Cancer Lett.
(1992)
H. Rochefort
Cathepsin D in breast cancer: a tissue marker associated with metastasis
Eur. J. Cancer
(1992)
J.R. Zabrecky et al.
The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells. SK-BR-3
J. Biol. Chem.
(1991)
C.I. Bargmann et al.
The neu oncogene encodes an epidermal growth factor receptor-related protein
Nature
(1986)
D.M. Barnes et al.
An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma
Br. J. Cancer
(1988)
M.S. Berger et al.
Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading
Cancer Res.
(1988)

E.M.J.J. Berns et al.

c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer

Cancer Res.

(1992)

N.D. Bloom et al.

Histological grading and prognosis in breast cancer

Br. J. Cancer

(1957)

A. Borg et al.

erbB-2 amplification in breast cancer with a high rate of proliferation

Oncogene

(1991)

M.M. Bradford

A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindings

Anal. Biochem.

(1976)

G. Contesso et al.

The importance of histologic grade in long-term prognosis of breast cancer: a study of 1010 patients, uniformly treated at the institut Gustave-Roussj

J. Clin. Oncol.

(1987)

L. Coussens et al.

Tyrosine kinase receptor with exstensive homology to EGF receptor shares chromosomal location with neu oncogene

Science

(1985)

E.R. Fisher et al.

Histologic grading of breast cancer

Pathology Ann.

(1980)

M. Garcia et al.

Monoclonal antibodies to the oestrogen-regulated M_r 52 000 glycoprotein: characterization and immunodetection in MCF7 cells

Cancer Res.

(1985)

M. Guerin et al.

Overexpression of either c-myc or $c -erb B -2 neu$ proto-oncogenes in human breast carcinomas: correlation with poor prognosis

Oncogene Res.

(1988)

M. Guerin et al.

Structure and expression of c-erbB-2 and EGF receptor genes in inflamatory and non inflamatory breast cancer: prognostic significance

Int. J. Cancer

(1989)

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net Significance of Wip1 overexpression in breast cancer: Strong association with hormone receptor expression and nodal metastasis
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Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades

Abstract

Eur. J. Cancer

Eur. J. Cancer

Eur. J. Cancer

Eur. J. Cancer

Cancer Lett.

Eur. J. Cancer

J. Biol. Chem.

The neu oncogene encodes an epidermal growth factor receptor-related protein

Nature

An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma

Br. J. Cancer

Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading

Cancer Res.

c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer

Cancer Res.

Histological grading and prognosis in breast cancer

Br. J. Cancer

erbB-2 amplification in breast cancer with a high rate of proliferation

Oncogene

A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindings

Anal. Biochem.

The importance of histologic grade in long-term prognosis of breast cancer: a study of 1010 patients, uniformly treated at the institut Gustave-Roussj

J. Clin. Oncol.

Tyrosine kinase receptor with exstensive homology to EGF receptor shares chromosomal location with neu oncogene

Science

Histologic grading of breast cancer

Pathology Ann.

Monoclonal antibodies to the oestrogen-regulated Mr 52 000 glycoprotein: characterization and immunodetection in MCF7 cells

Cancer Res.

Overexpression of either c-myc or c-erbB-2neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis

Oncogene Res.

Structure and expression of c-erbB-2 and EGF receptor genes in inflamatory and non inflamatory breast cancer: prognostic significance

Int. J. Cancer

Monoclonal antibodies to the oestrogen-regulated M_r 52 000 glycoprotein: characterization and immunodetection in MCF7 cells

Overexpression of either c-myc or $c -erb B -2 neu$ proto-oncogenes in human breast carcinomas: correlation with poor prognosis