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

Abstract

Background

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.

Conclusions

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.

Post author correction

Article Type: CASE REPORT

DOI:10.5301/ijbm.5000273

Authors

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

Disclosures

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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Authors

Affiliations

  • 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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