Riccardo Giannini et al., KRAS and BRAF genotyping of synchronous colorectal carcinomas. Oncology Letters

Authors: Riccardo Giannini, Cristiana Lupi, Fotios Loupakis, Adele Servadio, Chiara Cremolini, Elisa Sensi, Massimo Chiarugi, Carlotta Antoniotti, Fulvio Basolo, Alfredo Falcone, Gabriella Fontanini

Department of Surgery, University of Pisa, Pisa I-56126, Italy,
Unit of Surgical Pathology 3, Pisa University Hospital, Pisa I-56126, Italy,
Unit of Medical Oncology, Pisa University Hospital, Pisa I-56126, Italy


v?Ki?ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genotyping is required prior to anti?epidermal growth factor receptor monoclonal antibody therapy administered in cases of metastatic colorectal carcinoma (CRC). Thus, KRAS mutation screening is required for patient management. The present study reported the experience of KRAS/v?raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational screening on synchronous CRC pairs from 26 patients, which were defined as index lesions (ILs) and concurrent lesions (CLs) on the basis of tumor grade and dimension and their respective lymph node and distant metastases. Overall, KRAS mutations were present in 38.4% of patients, whereas BRAF mutations were present at a frequency of 11.5%. The genotyping of paired synchronous carcinomas indicated that 11 patients (42.3%) exhibited discordant KRAS mutational statuses in terms of the presence of a mutation in only one lesion of the pair or of two different mutations harbored by each lesion. BRAF mutations were present in the synchronous tumors of two cases, whereas in two other cases, only the IL or CL harbored mutant BRAF. Overall, the mutational statuses of distant and lymph node metastases confirm the genetic heterogeneity of synchronous primary tumors. These results highlighted the fact that adequate sampling and comprehensive testing, when feasible, is likely to optimize the decision?making process for treatment approaches, even in the relatively rare event of multiple synchronous lesions.

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