Annals of Oncology Advance Access originally published online on May 3, 2005
Annals of Oncology 2005 16(9):1557-1558; doi:10.1093/annonc/mdi261
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© 2005 European Society for Medical Oncology
Letter to the Editor |
Relevance of EGFR expression in colorectal cancer
In a recent issue of Annals of Oncology, Spano and colleagues reported their study of epidermal growth factor receptor (EGFR) expression by immunohistochemistry in 148 patients with colorectal cancer [1
]. The aim of this study was to analyse the relationship between EGFR reactivity and various histological and clinical characteristics and survival. Multivariate analysis found significant overexpression in the T3 stage while there was no impact on overall survival. This study suggests some comments. Regarding eventual prognostic impact, the first handicap is the high frequency (80%) of overexpression, which is consistent with other studies. EGFR has been extensively studied in many tumours providing a number of data. Although the authors discuss the expression of EGFR among the different sites of the colon, the notable variation in expression between primary and secondary sites has not been discussed [2]. As rapidly evoked in the last sentence, somatic mutations of the EGFR can play a major role, which has been clearly demonstrated in lung cancer [3, 4]. Until now, about 30 mutations have been determined within the kinase domain of EGFR in lung cancer with a wide variation of frequency according to several baseline characteristics including gender, ethnic group or histological subtypes. Thus, there is a relatively high frequency of mutations in women, in smokers, or in Japanese patients with non-small-cell lung cancer. EGFR mutations can enhance tyrosine kinase activity in response to EGF and increase the efficacy of anti-EGFR such as gefitinib or erlotinib [3, 4]. Increased expression of the multiple ligands, including EGF, TGF-
, epiregulin or amphiregulin, can also play a major role. To illustrate this, the prognostic value of EGFR in tumours of the head and neck, oesophagus, larynx, pancreas, lung, ovary, stomach or bladder was generally revealed when combined with increased EGF, TGF- or both. Of note, the prognostic value of EGFR expression remains unproven in breast and lung cancers. Moreover, the multiple signalling pathways following on from the activation of EGFR have their own impact on the tumoral potential. Thus, many actors interfere with EGFR, minimising its proper impact. In line with this, there is no apparent correlation between the expression of EGFR and response to certain targeted drugs, such as cetuximab, in metastatic colorectal cancer [5]. Tyrosine kinase inhibitors might interfere with the phosphorylation of several of these pathways such as Ras/ Raf/mitogen-activated protein kinase, or phosphatidylinositol 3'-kinase-Akt. Thus, eventual prognostic impact of EGFR might be reversed by targeted drugs such as illustrated in patients with metastatic breast cancer overexpressing HER2 and treated by trastuzumab. For all these reasons, the crude expression of EGFR probably does not belong to the most crucial biomarkers such as those selecting candidates to adjuvant systemic therapy among stage II patients, or predicting response to a given drug.
Hematology/Oncology Division, General Hospital of Annemasse, France
(* Email: alliotcfr{at}yahoo.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.
2. Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S. Epidermal growth factor receptor (EGFR) 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: 4720–4726.
3. Lynch TJ, Bell DW, Sordella R et al. Specific activating mutations in the epidermal growth factor receptor and responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129–2139.
4. Pao W, Miller V, Zakowski M et al. EGF receptor gene mutations are common in lung cancer from ‘never smokers’ and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101: 13306–13311.
5. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337–345.
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