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. 2011 Aug 1;17(15):5161-9.
doi: 10.1158/1078-0432.CCR-10-2666. Epub 2011 Jun 14.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

Siwen Hu-Lieskovan  1 , Daniel Vallbohmer, Wu Zhang, Dongyun Yang, Alexander Pohl, Melissa J Labonte, Peter P Grimminger, Arnulf H Hölscher, Robert Semrau, Dirk Arnold, Kathrin Dellas, Annelies Debucquoy, Karin Haustermans, Jean-Pascal H Machiels, Christine Sempoux, Claus Rödel, Matej Bracko, Vaneja Velenik, Heinz-Josef Lenz
Affiliations

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

Siwen Hu-Lieskovan et al. Clin Cancer Res. .

Abstract

Background: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

Methods: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

Results: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

Conclusion: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.

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Figures

Figure 1
Figure 1
EGF 61 polymorphism status and pCR.
See this image and copyright information in PMC

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