• © 2005 by American Society of Clinical Oncology

In Reply:

We thank Bralet et al for their comments to our article and particularly for the data they presented in their Letter to the Editor.

The question of an accurate, reliable detection of the biologic targets (epidermal growth factor receptor [EGFR] in this case) for targeted treatment modalities is, in fact, becoming increasingly crucial along with the expanding therapeutic options in this area.

In a series of 40 colorectal cancer patients, Bralet et al found an immunohistochemical expression of the EGFR in 38 primary tumors (95%), 23 metastatic lymph nodes (88%), and 51 liver metastases (79%), therefore substantially confirming a clinically significant variability of EGFR status according to the site of determination.

Moreover, a lack of correlation for EGFR expression is now described in a group of patients showing a proportion of EGFR-positive primary tumors (95%), sensibly higher than that described in our analysis, although the same cutoff for defining EGFR positivity (≥ 1% of cancer cells stained) is applied.

As suggested by Bralet et al, it is possible that this apparent discrepancy may be related to the use of different immunohistochemical methods. Nevertheless, other variables, for example the different sample size examined (40 patients v 99 patients in our article) to name one, could have also influenced this observation preventing us from drawing definitive conclusions.¹

More interestingly, the findings by Bralet et al seem to confirm the common need for further scientific insights into the molecular biology of the EGFR. This is of particular importance if we consider the close putative connection between the biologic mechanisms underlying the function of EGFR and the possibility of using it as a therapeutic target.

The biologic phenomenon that has been described in both studies (ie, lack of correlation of EGFR status between primary and metastatic sites) is possibly related to somatic genetic changes that still need to be fully investigated and that could also account for resistance to EGFR-targeted treatments in EGFR-positive tumors.

Now that anti-EGFR drugs are becoming more widely available for the treatment of colorectal cancer patients, clinical data along with molecular findings can help us to better define the biologic profile of “responding” tumors. In other words, it is time, once again, to get back from bedside to bench.