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Background: The k-Ras-protein shows in regard to its mutations status a predicitvity of the response after Cetuximab in patients with colon carcinoma. To our knowledge, not much is known, if k-RAS has also a predictivity in regard to different ways of metastasis. The goal of our investigations was the evaluation of k-Ras on primary non-metastatic colon cancer compared to lymphatic, hepatic and peritoneal metastasis. Methods: 98 patients with adenocarcinom of the colon and a postoperative pT2/3-status, who underwent surgical resection between 2006 and 2008 at the University of Tübingen had been included within the study collective. 53 patients had no metastasis (control group), while 45 patients revealed primary metastasis: lymphatic metastasis (n=20), hepatic spread (n=20) and multiple metastasize (n=5). After DNA-extraction, an amplification by ARMS-PCR was performed and the analysis of the mutation status was done by melting point analysis by Light-Cycler. Additionally sequencing of Exons 12 and 13 was performed in individual cases. Results: 29/98 (=30%) revealed a k-Ras-mutation. Out of these, 12 (=41%) had metastasis: 9 hepatic (=75%), 2 lymphatic (=17%) and 1 (=8%) multiple metastasis. Patients with k-Ras-mutation (n=29) showed a significant lower rate of lymphatic metastasis. (90% vs. 10%, p=0.031). The survival in accordance to the k-Ras mutation was not statistically significant (p=0.415). Conclusion: Patients with mutated k-Ras-gene in out patient population revealed no significant higher rate of metastasis (p=0.558), nor in regard to hepatic (p=0.090) or multiple locations (p=0.629). Our preliminary data assume, that the k-Ras mutation status has a predictive function on the rate of lymphatic metastasis in patients suffering from colon carcinoma (p=0.031). Follow-up-studies are demanded, if single mutations status might have an additional influence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 445. doi:1538-7445.AM2012-445

Background: cMYC as well as β-Catenin are downstream-targets of the Wnt-pathway and both have an important early function within the carcinogenesis and the progression of colon cancer. Additionally cMYC was found to be associated with a worse prognosis in other neoplasms. The goal of our investigations was the evaluation of the Wnt-pathway on primary non-metastatic colon cancer compared to lymphatic, hepatic and peritoneal metastasis in regard to the expression of cMYC and β-Catenin. Methods: 98 patients with adenocarcinom of the colon and a postoperative pT2/3-status, who underwent surgical resection between 2006 and 2008 at the University of Tübingen had been included within the study collective. 53 patients had no metastasis (control group), while 45 patients revealed primary metastasis: lymphatic metastasis (n=20), hepatic spread (n=20) and multiple metastasize (n=5). cMYC and β-Catenin was coloured on a Tissue-Micro-Array by immunohistochemistry with consecutive semiquantitative analysis. Results: 17 of 98 patients (17%) had been positive for cMYC. 5 out of these 17 (29%) revelaed metastasis. 16 out of the 17 cMYC-positive patients showed a nuclear accumulation of β-Catenin (94%) (p=0.027). 40 out of 81 (49%) cMYC negative patients revealed metastasis. No significant correlation between nuclear positive cMYC and the rate or kind of metastasis was found (p=0.133). In 29 out of 81 cMYC-negative patients (36%) a strong expression of β-Catenin was found. Conclusion: cMYC is well known for a worse prognosis in case of an overexpression in patients suffering from lymphoma. A correlation between the expression of cMYC and the kind of metastasis and / or survival nor prognosis in patients with colon cancer was not able to show (p=0.211). Additonally no correlation between the nuclear exprimed β-Catenin and different ways of metastasis was found (p=0.202). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 447. doi:1538-7445.AM2012-447