BACKGROUND: Previous studies indicate that drugs targeting the Epidermal Growth Factor Receptor (EGFR) signaling pathways can induce objective responses, prolong time to progression and improve survival of patients with metastatic colorectal cancer (mCRC). EGFR expression in the primary tumour may not predict response to these agents and data is conflicting regarding the correlation of EGFR expression in the primary tumour with the metastatic site. In other tumour sites, the presence of EGFR mutations was associated with efficacy in a subset of patients. OBJECTIVES: The goal of this study is to correlate tumour EGFR expression between primary and liver metastatic sites, and to assess the mutational status in the EGFR kinase domain. METHODS: This is a single center retrospective study of patients who underwent surgical resection of CRC, for whom paired paraffin-embedded tissue blocks of primary tumours and resected liver metastases were available. EGFR immunostaining and mutation analyses were preformed. RESULTS: Fifty six paired colorectal primaries and metastases were available for analysis. EGFR was detectable in 96.6% of the primary samples and in 89.7% of the metastatic samples. Perfect concordance in the intensity score between the primary and the metastases was found in 46.5% of the cases. While individual pairs were poorly concordant for intensity, the proportion of primaries with intense staining was similar to the proportion with intense staining in the metastatic samples. Overall survival did not correlate with either EGFR expression in the primary tumour, or with EGFR expression in the metastasis. There were 2 cases with mutations in the EGFR kinase domain. Both mutations were found in exon21 C>T. CONCLUSIONS: In this analysis, EGFR expression in the primary tumor site was not predictive of its level in the metastasis. EGFR expression levels in the primaries and in the metastases do not appear to be useful prognostic markers.
BACKGROUND: Previous studies indicate that drugs targeting the Epidermal Growth Factor Receptor (EGFR) signaling pathways can induce objective responses, prolong time to progression and improve survival of patients with metastatic colorectal cancer (mCRC). EGFR expression in the primary tumour may not predict response to these agents and data is conflicting regarding the correlation of EGFR expression in the primary tumour with the metastatic site. In other tumour sites, the presence of EGFR mutations was associated with efficacy in a subset of patients. OBJECTIVES: The goal of this study is to correlate tumourEGFR expression between primary and liver metastatic sites, and to assess the mutational status in the EGFR kinase domain. METHODS: This is a single center retrospective study of patients who underwent surgical resection of CRC, for whom paired paraffin-embedded tissue blocks of primary tumours and resected liver metastases were available. EGFR immunostaining and mutation analyses were preformed. RESULTS: Fifty six paired colorectal primaries and metastases were available for analysis. EGFR was detectable in 96.6% of the primary samples and in 89.7% of the metastatic samples. Perfect concordance in the intensity score between the primary and the metastases was found in 46.5% of the cases. While individual pairs were poorly concordant for intensity, the proportion of primaries with intense staining was similar to the proportion with intense staining in the metastatic samples. Overall survival did not correlate with either EGFR expression in the primary tumour, or with EGFR expression in the metastasis. There were 2 cases with mutations in the EGFR kinase domain. Both mutations were found in exon21 C>T. CONCLUSIONS: In this analysis, EGFR expression in the primary tumor site was not predictive of its level in the metastasis. EGFR expression levels in the primaries and in the metastases do not appear to be useful prognostic markers.
Authors: Max A Kruziki; Brett A Case; Jie Y Chan; Elizabeth J Zudock; Daniel R Woldring; Douglas Yee; Benjamin J Hackel Journal: Mol Pharm Date: 2016-10-10 Impact factor: 4.939
Authors: H Modjtahedi; S A Khelwatty; R S Kirk; A M Seddon; S Essapen; C A Del Vecchio; A J Wong; S Eccles Journal: Br J Cancer Date: 2012-02-07 Impact factor: 7.640
Authors: J A C M Goos; A C Hiemstra; V M H Coupé; B Diosdado; W Kooijman; P M Delis-Van Diemen; C Karga; J A M Beliën; C W Menke-van der Houven van Oordt; A A Geldof; G A Meijer; O S Hoekstra; R J A Fijneman Journal: Br J Cancer Date: 2014-07-01 Impact factor: 7.640
Authors: Javad Garousi; Ken G Andersson; Bogdan Mitran; Marie-Louise Pichl; Stefan Ståhl; Anna Orlova; John Löfblom; Vladimir Tolmachev Journal: Int J Oncol Date: 2016-02-02 Impact factor: 5.650
Authors: David J Stewart; Andrew A Stewart; Paul Wheatley-Price; Gerald Batist; Hagop M Kantarjian; Joan Schiller; Mark Clemons; John-Peter Bradford; Laurel Gillespie; Razelle Kurzrock Journal: Cancer Med Date: 2018-03-30 Impact factor: 4.452