Measurement of c‐erbb‐2 proteins in sera from patients with carcinomas and in breast tumor tissue cytosols: Correlation with serum tumor markers and membrane‐bound oncoprotein

Abstract

Using a commercial kit with antibodies against the ectodomain of c-erbB-2 protein, we detected c-erbB-2 immunoreactivity in human serum. We found that the percentages of patients with elevated serum c-erbB-2 immunoreactivities were 35, 21, and 9% in breast, prostate, and ovarian carcinoma, respectively. The majority of the elevated immunoreactivities were associated with sera containing highly elevated tumor markers with the highest in breast carcinoma (35%) and lowest in ovarian cancer (9%). Excellent correlations were also observed between the serum levels of c-erbB-2 immunoreactivity and the dominant tumor markers in serial specimens from individual cancer patients. We could also detect the c-erbB-2 immunoreactivity in the cytosols prepared from the breast tumor tissue for estrogen and progesterone receptor (ER & PgR) measurements using the same commercial kit for serum studies, and the intact c-erbB-2 oncoprotein (p185) in the extracts of the tissue membrane fractions with a different kit designed for tissue extract. The level of c-erbB-2 immunoreactivity in the cytosol from 124 human breast tumor specimens had an excellent correlation with the cell membrane concentrations of p185 (gamma = 0.89). Most of the elevated cytosol c-erbB-2 immunoreactivities were also found to associate with breast tumor specimens containing low concentrations of ER & PgR. It appears that measuring the c-erbB-2 immunoreactivity potentially could be used as a prognostic marker without performing tissue biopsies and also as a serum tumor marker for managing cancer patients.

Preoperative Plasma HER2 and Epidermal Growth Factor Receptor for Staging and Prognostication in Patients with Clinically Localized Prostate Cancer

“…Moreover, activation of the HER2 kinase signaling cascade can constitutively activate the androgen receptor and render prostate cancer cells refractory to androgen receptor inhibition in different model systems (29,34,37,38). Circulating levels of HER2 have been correlated with gene amplification and tissue overexpression (39,40). Taken together, these data suggest that preoperative plasma HER2 is a marker of early, clinically occult prostate cancer metastasis.…”

c-erbB-2 oncoprotein: A potential biomarker of advanced prostate cancer

“…Wu et al [17] first demonstrated that this protein is released in the circulation of prostate cancer patients. In their report, the distribution of tumor stages or disease statuses was not clarified.…”

“…They showed an increased level of the protein in sera of 3 of 12 patients with breast cancer, raising the possibility of using serum c-erbB-2 determination as a diagnostic and monitoring tool for c-erbB-2 positive carcinoma. Recently, Wu et al [17], reporting on the measurement of c-erbB-2 protein in sera from patients with prostate cancer, demonstrated that 21% (49/234) of the patients with prostate cancer had elevated serum levels of c-erbB-2 protein. In their report, however, the potential as a biomarker was not fully studied.…”

Tissue Expression and Serum Levels of HER-2/neu in Patients with Breast Cancer

“…The extracellular domain of the HER-2/»«/ receptor can be found in soluble form in the sera of patients with breast cancer [16][17][18][19]. The biological importance of solu ble HER-2/»«/ is highlighted by the fact that certain stud ies have indicated a close correlation of high HER-2/»«/ oncoprotein serum levels with an aggressive course of breast cancer [20].…”