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

2005; Elsevier BV; Volume: 16; Issue: 9 Linguagem: Inglês

10.1093/annonc/mdi262

1569-8041

Jean‐Philippe Spano, G. Milano,

HER2/EGFR in Cancer Research

Alliot and co-workers address relevant questions regarding our recent study which appeared in this journal [1.Spano J.P. Lagorce C. Atlan D. et al.Impact of EGFR expression on colorectal cancer patient prognosis and survival.Ann Oncol. 2005; 16: 102-108Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar]. In our study [1.Spano J.P. Lagorce C. Atlan D. et al.Impact of EGFR expression on colorectal cancer patient prognosis and survival.Ann Oncol. 2005; 16: 102-108Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar], 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. [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: 4772-4778Crossref PubMed Scopus (247) Google Scholar] 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 [3.Kluftinger A.M. Robinson B.W. Quenville N.F. et al.Correlation of epidermal growth factor receptor and c-erbB2 oncogene product to known prognostic indicators of colorectal cancer.Surg Oncol. 1992; 1: 97-105Crossref PubMed Scopus (74) Google Scholar, 4.Spaulding D.C. Spaulding B.O. Epidermal growth factor receptor expression and measurement in solid tumors.Sem Oncol. 2002; 29: 45-54Crossref PubMed Google Scholar]. Concerning our study, we used an EGFR composite score as described and validated by Goldstein and Armin [5.Goldstein N.S. 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: 1331-1346Crossref PubMed Scopus (373) Google Scholar], 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 [6.Chung K.Y. Shia J. Kemeny N.E. 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: 1803-1810Crossref PubMed Scopus (1067) Google Scholar]. 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 [7.Lynch T.J. Bell D.W. 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: 2129-2139Crossref Scopus (10139) Google Scholar]. Recent data exclude the presence of such mutations in colorectal cancer patients [8.Barber T.D. Vogestein B. Somatic mutations of EGFR in colorectal cancers and glioblastoma.Correspondence. N Engl J Med. 2004; 351: 2883Crossref PubMed Scopus (291) Google Scholar]. 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 [9.Spano J.P. Fagard R. Soria J.C. et al.Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives.Ann Oncol. 2005; 16: 189-194Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar], 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.