EGFR and cancer prognosis

doi:10.1016/S0959-8049(01)00231-3

European Journal of Cancer

Volume 37, Supplement 4, September 2001, Pages 9-15

https://doi.org/10.1016/S0959-8049(01)00231-3 Get rights and content

Abstract

Elevated levels of the epidermal growth factor receptor (EGFR), a growth-factor-receptor tyrosine kinase, and/or its cognate ligands have been identified as a common component of multiple cancer types and appear to promote solid tumour growth. This article examines the relationship between EGFR expression and cancer prognosis based on literature compiled on PubMed between 1985 and September 2000. More than 200 studies were identified that analysed relapse-free-interval or survival data directly in relation to EGFR levels in over 20 000 patients. Analysis of the data showed that 10 cancer types both express elevated levels of EGFR relative to normal tissues and have been studied in sufficient depth to allow sound judgements to be made concerning the association between EGFR and patient outlook. The EGFR was found to act as a strong prognostic indicator in head and neck, ovarian, cervical, bladder and oesophageal cancers. In these cancers, increased EGFR expression was associated with reduced recurrence-free or overall survival rates in 70% (52/74) of studies. In gastric, breast, endometrial and colorectal cancers, the EGFR provided more modest prognostic information, correlating to poor survival rates in 52% (13/25) of studies, while in non-small cell lung cancer (NSCLC), EGFR expression only rarely (3/10 studies) related to patient outlook. However, it is likely that the true prognostic significance of the EGFR has been underestimated as the published studies only assessed total cellular EGFR levels, rather than the activated form of the receptor, and were not standardised with regard to patient populations or assay methods. Finally, it is important to stress that failure to detect a prognostic significance for EGFR in any one cancer type does not necessarily preclude patients from benefiting from anti-EGFR therapies.

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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EGFR and cancer prognosis

Abstract

Introduction

Section snippets

Methodology

EGFR as a strong prognostic indicator

Discussion

Critical Rev. Oncol./Hematol.

J. Urol

Cell

Hum. Pathol.

Surg. Oncol

Gastroenterology