Abstract
4053 Background: K-Ras mutations in CRC primaries may predict resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, but we don´t know its behaviour in metastatic tissue. The aims of this study were: 1) Evaluate the grade of concordance of K-Ras status between primary and related metastatic samples 2) Establish a correlation between k-ras status and individual clinicopathological features Methods: K-ras mutations were retrospectively analysed in primary tumours of 124 patients and 138 related metastatic sites. The primary tumour site was colon in 87 patients and rectum in 37. Sites of metastases were liver (115 samples,83.3%) and lung (23 samples,16.7%). Some patients underwent surgery several times. We analyzed K-Ras point mutations in codons 12 and 13 by direct DNA sequencing from paraffin-embedded tumour and studied its relation with 13 clinicopathological features Results: K-Ras mutation was observed in 42(33.6%) primary tumours and in 52(39.1%) related metastatic sites, being the grade of concordance between primary and metastatic sites of 93% (95% CI: 97.5–88.3%). Discordance was observed in 9 (7%) patients: in 2, K-Ras status was wild type in metastatic site and expressed a mutational pattern in the primary tumour; vice versa, in 7, the mutation status was detected in the metastases meanwhile primary tumour was wild type. We also found statistically significative differences in mutation patterns regarding the site of the metastasic tissue: K-ras mutations were detected in 13 lung samples (61.9%) and in 39 liver samples (34.8%) (p=0.028). Of all the clinicopathological features analyzed we confirmed an increase of mutated K-ras status in tumours which had presented as perforation (p=0.044). No other relation with clinicopathological data was detected Conclusions: With this observational analysis, we confirm the high concordance (superior to 90%) between primary and related metastatic sites in terms of K-Ras status; for the first time, we have reported a higher mutational pattern in lung metastases than in liver disease, founds that may have important relevance regarding clinical/treatment decisions. For the realization of this study we received a grant from Amgen. No significant financial relationships to disclose.
Published Version
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