Mutation-based detection of molecular tumor margins in colorectal liver metastasis.

Le résumé fourni par la source

3610 Background: Defining adequate resection margins of liver metastasis especially after preoperative chemotherapy is based on empirically determined recommendations and random screening of macroscopic and microscopic tissue sections surrounding the liver metastasis. Mutations are highly specific for tumors and therefore can be used as a marker to accurately determine molecular tumor margins. Methods: In our study we evaluated 12 patients with metastatic colon cancer who underwent partial hepatectomy of 1-6 liver metastasis. Samples were obtained by 2-4 punch biopsies in different directions of surrounding liver tissue at 4, 8, 12 and 16 mm distance to the macroscopic tumor border. A total of 88 samples were analyzed. Tumor specific mutations including KRAS, PIK3CA, APC and TP53 were determined by sequencing tumor tissue. DNA was isolated from biopsies of surrounding liver tissue and analyzed by BEAMing, a highly sensitive PCR based method of mutation detection. Molecular results were correlated with microscopic tissue analysis and clinical data. Results: We were able to detect tumor DNA in surrounding liver tissue in 3 out of 12 patients with 4 samples positive at 4 mm and all samples negative at 8, 12 and 16 mm distance to the macroscopic tumor border with negative control samples. In average 1,047 mutant single stranded DNA fragments were found in 150,000 analyzed DNA fragments. 3 out of 10 patients with previous chemotherapy had positive molecular margins, whereas the 2 patients with naive liver tissue were tested negative for tumor DNA in their marginal zones. Conclusions: The measurement of tumor DNA in tissue is a highly sensitive molecular marker of tumor margins identifying consistently negative margins at > 0.4 cm distance to the macroscopic tumor border in all samples. Tumor DNA as a marker of molecular tumor margins could be helpful in determining accurate biological resection guidelines of liver metastasis and can help to understand the process of tumor reduction after preoperative chemotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Inostics Inostics Inostics

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.