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Evaluation of KRAS, NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists?
  1. Amélie Bourhis1,
  2. Caterina De Luca2,
  3. Mélanie Cariou3,
  4. Elena Vigliar2,
  5. Fanny Barel4,
  6. Floriana Conticelli5,
  7. Pascale Marcorelles1,
  8. Jean-Baptiste Nousbaum6,
  9. Michel Robaszkiewicz6,
  10. Laura Samaison7,
  11. Bogdan Badic6,
  12. Laurent Doucet1,
  13. Giancarlo Troncone2,
  14. Arnaud Uguen1,8
  1. 1 Pathology, CHRU de Brest, Brest, France
  2. 2 Public Health, University of Naples "Federico II", Naples, Italy
  3. 3 Registre des cancers digestifs du Finistère, Brest, France
  4. 4 Finistère, Ouest Pathologie, Brest, France
  5. 5 University of Naples "Federico II", Naples, Italy
  6. 6 CHRU de Brest, Brest, France
  7. 7 Ouest Pathologie, Quimper, France
  8. 8 Univ Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France, Univ Brest, Brest, France
  1. Correspondence to Dr Arnaud Uguen, Pathology, CHRU de Brest, Brest 80128, France; arnaud.uguen{at}


Aim We aimed to study the prognostic value of KRAS, NRAS, BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC)).

Methods We led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS, NRAS, BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry).

Results KRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)—proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00).

Conclusion Although being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC.

  • colorectal cancer
  • metastasis
  • molecular pathology

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  • Handling editor Runjan Chetty.

  • Contributors AU, GT, LD, MC, JBN and MR conceived and designed the study. FB, LD, LS and AB collected samples and pathological data and reviewed slides. AB, CDL, EV, FC, GT and LD performed molecular and immunohistochemistry analyses. AU, AB, GT and CDL analysed data, wrote, edited and reviewed the manuscript. MC, FB and BB provided clinical follow-up data. AU, GT, AB, GT, CDL and PM wrote and reviewed the manuscript. All authors gave final approval for publication.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Biocartis company has provided Idylla dedicated cartridges for this study but has not taken part in data interpretation or manuscript writing in this work.

  • Patient consent for publication Not required.

  • Ethics approval Data were registered in the digestive cancer registry of Finistere database certified by the French National Committee of Registries and the present study was conducted in accordance with the Declaration of Helsinki and after approval by our institutional review board with tumour samples registered in a tumour tissue collection (CHRU Brest, CPP n° DC—2008–214).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. See tables for data relevant to the study.