The long term prognostic significance of c-erbB-2 in primary breast cancer

Abstract

SummaryThe expression of the c-erbB-2 oncogene has been evaluated using an immunohistochemical technique with the 21N polyclonal antibody in paraffin embedded tissue from 465 patients treated between the years [1975][1976][1977][1978][1979][1980][1981] for Stage I and II breast cancer. One hundred and four (22%) patients exhibited positive staining. This was not associated with any other variables. Expression of the oncogene was associated with significantly poorer survival which was independent of other tumour variables.The proto-oncogene c-erbB-2 encodes a protein present at the cell surface which has considerable homology with the epidermal growth factor receptor EGFR (Coussens et al., 1985). Although originally identified as an oncogene in chemically induced neuroblastomas in rats (Pahdy et al., 1982;Bargmann et al., 1986), recent interest has focused on its role in human breast cancer. Studies on cell lines derived from human mammary carcinomas have demonstrated that c-erbB -2 can be overexpressed by several mechanisms including gene amplification (Kraus et al., 1987) and this is present in up to 30% of human breast cancers (Slamon et al., 1987;van de Vijver et al., 1987;Varley et al., 1987;Zhou et al., 1987).The development of both polyclonal and monoclonal antibodies to the oncoprotein has allowed its distribution to be evaluated in histological sections, and its presence and clinical significance to be correlated with amplification of its gene and expression of its mRNA (Venter et al., 1987;van de Vijver et al., 1987;Slamon et al., 1989;Gusterson et al., 1988). These studies have confirmed that both gene amplification and increased transcription of its mRNA are associated with expression of this putative receptor at the cell surface in patients with breast cancer. One study though has reported that 20% of patients expressing this receptor failed to exhibit a corresponding amplification of its gene (Berger et al., 1988) and has concluded that other mechanisms may also be of importance in allowing it to be expressed.In both molecular studies and those based on immunological detection of the protein expression of the receptor has been associated with the spread of tumour to the axillary lymph nodes, to the number of nodes involved (Zhou et al., 1987;Slamon et al., 1987Slamon et al., , 1989, larger tumours (van de Vijver et al., 1987) and with poor histological grade (Berger et al., 1988). However, the number of patients assessed in these studies is variable and some have contained too few patients to evaluate the statistical significance of the data. Reports of its clinical significance have been conflicting, with some investigators noting a poorer prognosis in patients expressing the protein (Slamon et al., 1989;Wright et al., 1989a; Lovekin et al., 1989) and others reporting little difference (Barnes et al., 1988;Zhou et al., 1989; Alli et al., 1988;Gusterson et al., 1988 obtained. In addition, blocks were obtained from 100 patients with both benign fibrocystic disease and fibroadenomas who had undergon...

Prognostic Association of C-Erbb-2 Oncogene Amplification and Protein Overexpression in Human Breast Cancer Using Archival Tissues a Comparative Study

“…Ovet-expression of c-erbB-2 protein, on the other hand, was strongly correlated with DFS and S in our patients. Although some earlier studies have failed to show an association between prognosis and overexpression of the c-erbB-2 protein detected by IHC (14,15,20), there is a gencral agreement among more recently published reports that overexpression of the c-erbB-2 gene product is related to poor survival in breast cancer (10)(11)(12)(13)(33)(34)(35)(36). Our results are consistent with this emerging consensus.…”

Expression of c-erbB-2 protein in papillary thyroid carcinomas

“…c-erbB-2 protein overexpression is currently being evaluated as a potential risk factor in breast cancer patients Lovekin et al, 1991;O'Reilly et al, 1991;Winstanley et al, 1991).…”

c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival

“…Southern, Northern and Western blots, as well as immunochemistry and fluorescence in situ hybridization (FISH), can be assessed in archival breast cancer specimens to detect c-erbB-2 amplification or overexpression, although FISH was recently found to be superior to all methodologies in fixed paraffinembedded tissue (Pauletti et al, 1996). However, whatever the method used, fixation and paraffin embedding are responsible for a certain loss of antigenicity, as shown by the comparison of immunodetections performed on paraffin sections and on frozen sections (Tandon et al, 1989;Winstanley et al, 1991;Heatley et al, 1993 Quantitative immunocytochemistry has already been developed on a different system for c-erbB-2 ICAs (Baak et al, 1991;Bacus et al, 1990a, b;Charpin et al, 1992Charpin et al, , 1993Press et al, 1993). In one study (Press et al, 1993), the quantitative c-erbB-2 ICAs were related to the patients' follow-up.…”

“…This report and the following one (Slamon et al, 1989) demonstrated that c-erbB-2 was significantly correlated with the clinical outcome of patients with metastatic axillary lymph nodes. Some further publications demonstrated that c-erbB-2 amplification and overexpression were significant prognostic indicators, independent of other current prognostic factors (Van de Vijver et al, 1988;Walker et al, 1989;Tandon et al, 1989;Wright et al, 1989;McCann et al, 1991;Paterson et al, 1991;Winstanley et al, 1991). Other studies, however, could not demonstrate that c-erbB-2 amplification or overexpression did have prognostic significance (Shou et al, 1989;Heintz et al, 1990;Kury et al, 1990;Clark et al, 1991;McCann et al, 1991;Ravdin et al, 1995).…”

“…This controversy may arise from variations in the series size, technical procedures and/or statistical methods of analysis (Ravdin et al, 1995;Pauletti et al, 1996). In particular, discrepancies in immunocytochemical studies may result from tissue fixation (Slamon et al, 1987(Slamon et al, , 1989Tandon et al, 1989;Clark et al, 1991;Paterson et al, 1991;Winstanley et al, 1991;Piffanelli et al, 1996) and from the lack of standardized means of evaluating immunostaining (Tandon et al, 1989;Charpin et al, 1993).…”