Discordance in RAS mutations between primary colon tumor and metastases: a real event or a matter of methodology?



Analysis of K- and N-RAS mutations is mandatory before planning treatment of metastatic colorectal cancer, because only RAS wild-type (WT) patients can benefit from treatment with anti-EGFR monoclonal antibodies (cetuximab and panitumumab).

Case report

Here we report the case of a 69-year-old male patient affected by metastatic sigmoid cancer. He underwent left hemicolectomy, and histology diagnosed a well-differentiated, pT4, node-positive adenocarcinoma; KRAS analysis performed with direct sequencing identified a mutation in exon 2 of the KRAS gene (GGT->GTT). After first-line chemotherapy with FOLFOX6 plus bevacizumab, the patient underwent surgical resection of residual liver metastases. Histology showed metastatic deposits from colic adenocarcinoma with extensive coagulative necrosis. Mutational analysis of the KRAS gene was also performed on liver metastases by pyrosequencing assay, and no mutation was identified. Due to the discordant results (GGT->GTT exon 2 KRAS mutation in the primary tumor, and KRAS-WT in the liver metastases), mutational analysis on liver metastasis was repeated using next-generation sequencing and enriching the sample in tumor cells by manual microdissection; the same type of mutation of the primary tumor (GGT->GTT exon 2 KRAS gene) was confirmed.


Accurate tissue sampling and adequately sensitive assays are essential to correctly identify colorectal cancer patients who can be treated with an anti-EGFR monoclonal antibody.

Int J Biol Markers 2017; 32(4): e474 - e477

Article Type: CASE REPORT



Alfonso De Stefano, Mario Rosanova, Umberto Malapelle, Maurizio Martini, Stefano De Falco, Laura Attademo, Giovanni Fiore, Tonia Cenci, Claudio Bellevicine, Sabino De Placido, Giancarlo Troncone, Chiara Carlomagno

Article History


Financial support: No grants or funding have been received for this study.
Conflict of interest: None of the authors have any conflict of interest with the present manuscript.

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  • Department of Clinical Medicine and Surgery, Federico II University, Naples - Italy
  • Department of Public Health, Federico II University, Naples - Italy
  • Division of Pathological Anatomy and Histology, Catholic University of the Sacred Heart, Rome - Italy

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