Letter to the Editor

British Journal of Cancer (2005) 93, 1316–1316. doi:10.1038/sj.bjc.6602843 www.bjcancer.com
Published online 18 October 2005

Is membranous location of EGFR or EGFRvIII immunostaining associated with good prognosis in renal cell carcinoma?

H Modjtahedi1 and M P Cunningham1

1Division of Oncology, Postgraduate Medical School, University of Surrey, Guildford GU2 7WG, UK

Correspondence: Dr H Modjtahedi, E-mail: H.Modjtahedi@Surrey.ac.uk

Sir,

We read with great interest the published article by Kallio et al (2003) in the British Journal of Cancer on the association between the location of EGFR immunostaining and overall survival in renal cell carcinoma (RCC) patients. In this paper, the authors have reported that overall survival was significantly longer (P=0.004) in patients with prominent membranous EGFR expression compared to patients with either EGFR-negative tumours or tumours with predominantly cytoplasmic EGFR staining (Kallio et al, 2003). This is an important finding, as the expression of membranous EGFR has often been associated with a poor prognosis in cancer patients (Lager et al, 1994; Moch et al, 1997), while other studies have found either no association between EGFR expression and prognosis (Hofmockel et al, 1997) or more recently an association between the expression of cytoplasmic EGFR and poor prognosis in RCC patients (Langner et al, 2004).

To our knowledge, the paper by Kallio et al is the first paper to describe an association between prominent membranous EGFR immunostaining and longer overall survival in RCC patients. However, there is a conflicting statement in the Materials and Methods section of the paper by Kallio et al that prevents us from accepting their conclusion and the authors need to clarify/rectify accordingly. In the immunohistochemical staining section of the Materials and Methods, Kallio et al stated the use of a polyclonal rabbit anti-EGFR variant III antibody (EGFRvIII) for EGFR immunostaining. The EGFRvIII is a ligand-independent, constitutively active and mutated form of EGFR (Pederson et al, 2001). Did the author use the rabbit anti-EGFRvIII antibody in their study and if so does it crossreact with the EGFR? Could Kallio et al clarify/rectify whether the prominent membranous EGFRvIII immunostaining in that study was associated with a good prognosis in patients with RCC? While no clear association has been found between the expression of the EGFR and response to the EGFR inhibitors in cancer patients, including patients with RCC, the expression of membranous EGFR and/or EGFRvIII in RCC patients would, however, make them an ideal target for therapy with the anti-EGFR antibodies (Modjtahedi et al, 2003; Dawson et al, 2004; Rowinsky et al, 2004; Dancey, 2004). We would appreciate clarification from Kallio et al.

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References

  1. Dancey JE (2004) Epidermal growth factor receptor and epidermal growth factor receptor therapies in renal cell carcinoma: do we need a better mouse trap? J Clin Oncol 22: 2975–2977 | Article | PubMed | ISI | ChemPort |
  2. Dawson NA, Guo C, Zak R, Dorsey B, Smoot J, Wong J, Hussain A (2004) A phase II trial of gefitinib (Iressa, ZD1839) in stage IV and recurrent renal cell carcinoma. Clin Cancer Res 10: 7812–7819 | Article | PubMed | ISI | ChemPort |
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  4. Kallio JP, Hirvikoski P, Helin H, Kellokumpu-Lehtinen P, Luukkaala T, Tammela TL, Martikainen PM (2003) Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma. Br J Cancer 89: 1266–1269 | Article | PubMed | ISI | ChemPort |
  5. Lager DJ, Slagel DD, Palechek PL (1994) The expression of epidermal growth factor receptor and transforming growth factor alpha in renal cell carcinoma. Mod Pathol 7: 544–548 | PubMed | ISI | ChemPort |
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  8. Modjtahedi H, Moscatello DK, Box G, Green M, Shotton C, Lamb DJ, Reynolds LJ, Wong AL, Dean C, Thomas H, Eccles S (2003) Targeting of cells expressing wild type EGFR and type-III mutant EGFR (EGFRvIII) by anti-EGFR mAbs ICR62: a two pronged attack for tumour therapy. Int J cancer 105(2): 273–280 | Article | PubMed | ISI | ChemPort |
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