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Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis

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Abstract

Purpose

After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice.

Methods/patients

We classified 105 patients with resected CRC (stage I–III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated.

Results and conclusions

RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.

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Author information

Authors and Affiliations

  1. Medical Oncology Department, Hospital de Requena, av/Casablanca s/n, 46340, Requena (Valencia), Spain

    M. Gil-Raga

  2. Molecular Oncology Laboratory, CIBERONC, Fundación Investigación Hospital General Universitario de Valencia, Valencia, Spain

    E. Jantus-Lewintre & S. Gallach

  3. Biotechnology Department, CIBERONC, Universitat Politécnica de València, Valencia, Spain

    E. Jantus-Lewintre

  4. Centre for Quality and Change Management, Universitat Politècnica de València, Valencia, Spain

    V. Giner-Bosch

  5. Department of Surgery, Hospital de Sagunto, Valencia, Spain

    A. Frangi-Caregnato

  6. Medical Oncology Department, Hospital General Universitario de Valencia, Valencia, Spain

    M. J. Safont-Aguilera & C. Camps-Herrero

  7. Medical Oncology Department, Hospital Arnau de Vilanova, Valencia, Spain

    J. Garde-Noguera

  8. Anatomic Pathology Department, Hospital de Sagunto, Valencia, Spain

    E. Zorraquino-Pina

  9. Medical Oncology Department, Hospital de Sagunto, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain

    M. García-Martínez

  10. Department of Medicine, CIBERONC, Universitat de Valencia, Valencia, Spain

    C. Camps-Herrero

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  1. M. Gil-Raga
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Correspondence to M. Gil-Raga.

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Conflict of interest

All authors declare that they have no competing interest.

Research involving human participants and/or animals/ethical approval

All procedures performed in studies involving human participants were in accordance with the Clinical Research Ethics Committee of General University Hospital of Valencia and by The Research Committee of Hospital of Sagunto, in accordance with the Declaration of Helsinki (1964), the Good Clinical Practices and local ethical and legal requirements (Spanish laws). This study complied with all applicable regulations for human participant studies. All authors reviewed and approved the final manuscript.

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Prior to study entry, all patients provided written informed consent according to the local ethics committee regulations.

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Gil-Raga, M., Jantus-Lewintre, E., Gallach, S. et al. Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis. Clin Transl Oncol 20, 1422–1429 (2018). https://doi.org/10.1007/s12094-018-1874-8

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  • DOI: https://doi.org/10.1007/s12094-018-1874-8

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