Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance

Abstract

Summary A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain.

Prospective evaluation of prognostic factors in operable breast cancer

“…The present study found no evidence that EGFR measurements offer prognostic information additional to that provided by ER concentration, node status and tumour grade. These findings are also in line with our previous study (Hawkins et al, 1991) and the results of multivariate analyses by Dutch workers (Koenders et al, 1993;Foekens et al, 1989) and may perhaps relate to factors other than the four listed above. In the present study, in order to be able to include as many tumours (irrespective of size) as possible, we changed our method for EGFR assay from a multiple-dose one with Scatchard analysis (Hawkins et al, 1991) to a single saturating-dose assay.…”

“…We have selected four putative biochemical indices of prognosis and evaluated them in a prospective study. The putative markers chosen were the oestrogen receptor (ER), the epidermal growth factor receptor (EGFR), cathepsin D (cath D) and cyclic AMP-binding protein(s) (c-AMP-b).The oestrogen receptor, a nuclear protein (Mr 66 kDa) has been shown to relate to both endocrine sensitivity (Jensen, 1975) and prognosis in multiple studies, including our own previous work (Humeniuk et al, 1982;Hawkins et al, 1987aHawkins et al, , 1991, although some consider that it is only of prognostic significance in the early years after treatment (e.g. Saez et al, 1983).…”

“…The oestrogen receptor, a nuclear protein (Mr 66 kDa) has been shown to relate to both endocrine sensitivity (Jensen, 1975) and prognosis in multiple studies, including our own previous work (Humeniuk et al, 1982;Hawkins et al, 1987aHawkins et al, , 1991, although some consider that it is only of prognostic significance in the early years after treatment (e.g. Saez et al, 1983).…”

“…Determination of EGFR EGFR was determined on the 'membranes' pellet remaining after high-speed centrifugation of the homogenate used for ER assay, by modification of a method described previously (Hawkins et al, 1991 (300 nM) of non-radioactive EGF. The tubes were mixed and incubated (total volume 0.4 ml) for 90 min at 26°C before separation of free and bound EGF by the addition of 0.5 ml IgG solution (0.5% w/v) and 1.0 ml of polyethylene glycol (25% v/v), incubation on ice for 15 min and centrifugation.…”

“…In our experience, this SSD method measures only highaffinity sites by comparison with the multidose saturation method we used previously (Hawkins et al, 1991) [correlation between the assays: 1 (SSD) = 1.15 x (Scatchard) + 0.72 fmol mg-protein, Spearman's r = 0.70, n =24 tissues]. In our hands, the use of higher concentrations of [251I]EGF (1 nM) in such an assay (Nicholson et al, 1988) yielded measurements of a mixture of high-and some low-affinity sites.…”