Reply to the "Letter to the Editor on ‘Relevance of EGFR expression in colorectal cancer’" by C. Alliot (Ann Oncol 2005; 16: 1557)

Alliot and co-workers address relevant questions regarding our recent study which appeared in this journal [1Go]. In our study [1Go], we analysed epidermal growth factor receptor (EGFR) expression and its relationship with the main histological and clinical characteristics in a group of colorectal cancer patients. We found that EGFR overexpression was significantly associated with tumor stage, especially T3. Nevertheless, we did not analyse the expression of EGFR in case of recurrent disease and we did not have samples available to compare EGFR expression between primary and metastatic sites of the tumour. We agree with the comments by Alliot and co-workers and it is clear that it would be particularly interesting to perform such an analysis bearing in mind the recent data published by Scartozzi et al. [2Go] emphasising changes in EGFR immunohistocompatibility (IHC) expression between primary- and metastatic-stage disease although these results must, however, be taken with caution knowing the variability in EGFR determination by IHC [3Go, 4Go]. Concerning our study, we used an EGFR composite score as described and validated by Goldstein and Armin [5Go], which remains one of the most accurate scoring systems currently defined for IHC. Above all, we consider that the variability of treatment decision based on EGFR expression measured by IHC remains to be established since there are reports indicating response rate to EGFR-targeting drugs in EGR negative colorectal cancer patients by IHC [6Go].

The second point advocated by Alliot and co-workers is related to EGFR mutations that can be predictive of response to EGFR targeted therapies. We agree with the view that some EGFR mutations may favour the activity of anti-EGFR drugs, but for the moment these mutations are essentially reported in lung cancer patients [7Go]. Recent data exclude the presence of such mutations in colorectal cancer patients [8Go]. In conclusion, efforts must be made to evaluate how we can optimise patient selection for EGFR targeting, especially for colorectal cancer patients. As we underlined in a recently published study [9Go], other biomarkers are necessary to be evaluated besides EGFR expression itself and, as mentioned by Alliot and co-workers, p-AKT expression, MAPK expression or EGFR amplification are all good candidates for this purpose.

J. P. Spano1,* and G. Milano2

1 SOMPS, Université Pierre et Marie Curie, Paris; 2 Laboratoire d'Oncopharmacologie, CAC Antoine Lacassagne, Nice, France

(* Email: jean-philippe.spano{at}psl.ap-hop-paris.fr)

References

1. Spano JP, Lagorce C, Atlan D et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 2005; 16: 102–108.[Abstract/Free Full Text]

2. Scartozzi M, Bearzi I, Berardi R et al. Epidermal growth factor receptor status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 2004; 22: 4772–4778.[Abstract/Free Full Text]

3. Kluftinger AM, Robinson BW, Quenville NF et al. Correlation of epidermal growth factor receptor and c-erbB2 oncogene product to known prognostic indicators of colorectal cancer. Surg Oncol 1992; 1: 97–105.[CrossRef][Medline]

4. Spaulding DC, Spaulding BO. Epidermal growth factor receptor expression and measurement in solid tumors. Sem Oncol 2002; 29: 45–54.

5. Goldstein NS, Armin M. Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 2001; 92: 1331–1346.[CrossRef][ISI][Medline]

6. Chung KY, Shia J, Kemeny NE et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005; 23: 1803–1810.[Abstract/Free Full Text]

7. Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 351: 2129–2139.[Free Full Text]

8. Barber TD, Vogestein B. Somatic mutations of EGFR in colorectal cancers and glioblastoma. Correspondence. N Engl J Med 2004; 351: 2883.[Free Full Text]

9. Spano JP, Fagard R, Soria JC et al. Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. Ann Oncol 2005; 16: 189–194.[Abstract/Free Full Text]





This Article
Full Text (PDF)
All Versions of this Article:
16/9/1558    most recent
mdi262v1
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Spano, J. P.
Articles by Milano, G.
PubMed
PubMed Citation
Articles by Spano, J. P.
Articles by Milano, G.