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Medline ® Abstract for Reference 62

of 'Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations'

EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer.
Ålgars A, Lintunen M, Carpén O, Ristamäki R, Sundström J
Br J Cancer. 2011;105(2):255. Epub 2011 Jun 21.
BACKGROUND: Only 40-70% of metastatic colorectal cancers (mCRCs) with wild-type (WT) KRAS oncogene respond to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. EGFR amplification has been suggested as an additional marker to predict the response. However, improved methods for bringing the EGFR analysis into routine laboratory are needed.
METHODS: The material consisted of 80 patients with mCRC, 54 of them receiving anti-EGFR therapy. EGFR gene copy number (GCN) was analysed by automated silver in situ hybridisation (SISH). Immunohistochemical EGFR protein analysis was used to guide SISH assessment.
RESULTS: Clinical benefit was seen in 73% of high (≥4.0) EGFR GCN patients, in comparison with 59% of KRAS WT patients. Only 20% of low EGFR GCN patients responded to therapy. A high EGFR GCN number associated with longer progression-free survival (P<0.0001) and overall survival (P=0.004). Together with KRAS analysis, EGFR GCN identified the responsive patients to anti-EGFR therapy more accurately than either test alone. The clinical benefit rate of KRAS WT/high EGFR GCN tumours was 82%.
CONCLUSION: Our results show that automated EGFR SISH, in combination with KRAS mutation analysis, can be a useful and easily applicable technique in routine diagnostic practise for selecting patients for anti-EGFR therapy.
Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, PO Box 52, Turku FIN-20521, Finland. annika.algars@utu.fi