In colorectal cancer (CRC) oncogenic mutations such as KRAS alterations, are considered standard molecular biomarkers that predict the clinical benefit for targeted intervention with epidermal growth factor receptor (EGFR) inhibitors. In addition, these mutations are associated with specific anatomical area in colon tumor development, as BRAF mutations with the microsatellite instability (MSI). In this translational study, we aimed to assess the mutation frequencies of the EGFR (hotspot area and polyadenine deletions A13_del), KRAS, BRAF V600E , and PIK3CA oncogenes in a series of 280 CRC patients. MSI phenotypes are also considered in this series. All patients' clinicopathological data were assessed for statistical analysis and its associations were validated. We verified multiple associations between oncogenic mutations and determined clinicopathological tumor features (1) EGFR A13_deletions are associated with right colon carcinoma (Po0.005), mucinous histotype (P ¼ 0.042), G3 grading (P ¼ 0.024), and MSI status (Po0.005); (2) PIK3CA mutations are related mucinous histotype (P ¼ 0.021); (3) KRAS G12 and KRAS G13 mutations are correlated, respectively, with the left and right colon cancer development (Po0.005), and finally (4) MSI is associated with right colon tumors (Po0.005). Mostly, we verified a higher frequency rate of the KRAS G13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRAS G12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right vs left colon cancer are associated with specific molecular characteristics. These evidences, in association with clinicopathological data, can delineate novel approaches for the CRC classification and targeted intervention.

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e22037 Background: Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p<0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p<0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRASG12 and KRASG13mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p<0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p<0.005). Conclusions: Mostly, we verified a high frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.