EGFR and cancer prognosis
Introduction
The growth and development of cancer cells is thought to occur through multiple genetic events that cause fundamental changes in the pathways regulating cell differentiation, proliferation, survival and mobility. Activation of the proto-oncogene encoding the epidermal growth factor receptor (EGFR), a growth-factor-receptor tyrosine kinase, may contribute to the transformation of cellular phenotypes and provide tumour cells with substantial growth and survival advantages (reviewed in Ref. [1]). Over the last 20 years, elevated levels of the EGFR and its cognate ligands (which include EGF and transforming growth factor (TGF)-α) have been identified as a common component of numerous cancer types. In many cases aberrant EGFR activation, mediated primarily through changes in gene amplification and autocrine stimulation, appears to be an important factor in tumorigenesis, as well as an essential driving force for the aggressive growth behaviour of cancer cells [2]. Increased EGFR expression is therefore likely to be a strong prognostic feature in multiple tumour types, and the inhibition of its cellular actions appears to produce substantial therapeutic benefits.
Section snippets
Methodology
In this light, the current overview examines the association between EGFR expression and cancer prognosis. Relevant literature published between 1985 and September 2000 was identified on PubMed using the keywords epithelial growth factor, EGFR and EGF-R in combination with individual tissue or cancer types. Over 200 relevant references were identified from PubMed containing information about more than 20 000 patients. However, only general conclusions should be made from this retrospective
EGFR as a strong prognostic indicator
In head and neck, ovarian, cervical, bladder and oesophageal cancer (e.g. 3, 4, 5, 6, 7, respectively), the association between elevated EGFR levels (Fig. 1) and poor patient outlook is particularly strong. Of the 74 studies in these cancer types, 70% showed that increased EGFR expression correlated with a reduction in recurrence-free survival or overall survival rates (Table 1).
In a number of investigations with these cancer types, the magnitude of the EGFR effect on survival was highly
Discussion
Analysis of the existing literature on EGFR and prognosis clearly indicates that elevated levels of EGFR are correlated with poor patient outlook in many different cancer types. As mentioned above, this analysis is likely to underestimate the true predictive significance of the EGFR due to inconsistencies in the assay methods used and the heterogeneity of the patient populations between studies. The lack of a standardised assay for determining tumour EGFR status is particularly problematic.
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