Detection of C-ERBB-2 Related Protein in Sera from Breast Cancer Patients Relationship to ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour

Abstract

The level of a c-erbB-2 related protein was determined in sera from 168 breast carcinoma patients, 12 females with benign breast disease, and 66 female controls using an ELISA (enzyme linked immunosorbent assay) kit. Elevated c-erbB-2 related protein level was detected in one of 13 preoperative sera (8%), two of 62 postoperative sera from patients without recurrent disease (3%), and 55 of 93 sera collected at recurrent disease (59%). Elevated serum levels were detected significantly more often in patients with distant metastases than in patients with recurrent disease restricted to loco-regional areas (68% versus 19%). Presence of elevated serum level was associated with ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour. None of the patients who had normal ERBB2 gene copy number in tumour had elevated serum levels. Although the usefulness in postoperative prediction of the presence of micrometastases is somewhat questionable, the results suggest c-erbB-2 related protein to represent a novel tumour marker in serum and other body fluids from breast cancer patients at the time of diagnosis and during treatment monitoring.

Study of pretreatment serum levels of HER‐2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma

“…Therefore, the availability of a reliable method for measuring circulating levels of HER-2/neu ECD is an interesting opportunity to assess the diagnostic and prognostic role of HER-2/neu overexpression in patients with tumor that are not easily accessible for biopsy. Elevated serum levels of HER-2/neu protein have been correlated with HER-2/neu gene amplification and tissue overexpression in patients with breast carcinoma 26 and gastric carcinoma. 39 In addition, in patients with advanced breast carcinoma, elevated pretreatment levels of the protein were associated with a shorter time to disease progression and overall survival duration, whereas low pretreatment levels were the most powerful predictor of response to hormonal therapy.…”

“…24 In some patients, elevated protein serum levels also were detectable prior to the time of clinical diagnosis. 25 High HER-2/neu oncoprotein circulating levels have been correlated with tissue overexpression 26,27 and have been associated with a poor survival outcome in patients with breast carcinoma. 28 -30 A study that considered a heterogeneous group of lung adenocarcinomas also found a good correlation between HER-2/neu expression in tissue and serum levels.…”

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

“…These results are similar to outcomes of studies showing that changes in HER-2 overexpression do not correlate with clinical outcome. [17][18][19][20] Chemotherapy and cytokine treatments used to mobilise haematopoietic stem cells into blood can also mobilise tumour cells and the observed increase in the number of patients with circulating HER-2 after ICT may be related to this effect. 30,31 ICT may also increase the amount of soluble HER-2 fragment released from tumours containing HER-2 overexpressing cells.…”

“…[7][8][9][10][11][12][13][14] Although HER-2 oncoprotein overexpression correlates with reduced patient survival, few studies have evaluated the incidence of HER-2 overexpression in patients with metastatic breast cancer (MBC) and examined whether increased levels of this protein indicate a poorer prognosis and/or reduced responsiveness to systemic treatment. [14][15][16][17][18][19][20][21][22][23][24] In these studies, 30-50% of patients with MBC had elevated levels of circulating (plasma, serum) extracellular domain of HER-2. [14][15][16][17][18][19] Overexpression correlates with an increased tumour burden and reduced survival.…”

“…[14][15][16][17][18][19][20][21][22][23][24] In these studies, 30-50% of patients with MBC had elevated levels of circulating (plasma, serum) extracellular domain of HER-2. [14][15][16][17][18][19] Overexpression correlates with an increased tumour burden and reduced survival. [14][15][16]18,[22][23][24][25] Since EIA (enzyme immunoassay) is a relatively simple assay commonly used in clinical medicine, the possibility that elevated levels of extracellular HER-2 could indicate poor prognosis in patients with MBC is of particular interest.…”