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

Mireia Gil Raga; Eloisa Jantus Lewintre; Sandra Gallach; Vicent Giner Bosch; Andrés Frangi; María José Safont; Javier Garde Noguera; E. Zorraquino Pina; M. García Martínez; Carlos Camps Herrero

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

M. Gil-Raga ^[5] ; E. Jantus-Lewintre ^[6] ; S. Gallach ^[6] ; V. Giner-Bosch ^[1] ; A. Frangi-Caregnato ^[2] ; M. J. Safont-Aguilera ^[3] ; J. Garde-Noguera ^[4] ; E. Zorraquino-Pina ^[2] ; M. García-Martínez ^[2] ; C. Camps-Herrero ^[3]
1. [1] Universidad Politécnica de Valencia
  
  Universidad Politécnica de Valencia
  
  Valencia, España
2. [2] Hospital de Sagunto
  
  Hospital de Sagunto
  
  Sagunto/Sagunt, España
3. [3] Hospital General Universitario de Valencia
  
  Hospital General Universitario de Valencia
  
  Valencia, España
4. [4] Hospital Arnau de Vilanova
  
  Hospital Arnau de Vilanova
  
  Valencia, España
5. [5] Hospital de Requena, España
6. [6] Fundación Investigación Hospital General Universitario de Valencia, España
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Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 20, Nº. 11 (November 2018), 2018, págs. 1422-1429
Idioma: inglés
DOI: 10.1007/s12094-018-1874-8
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Resumen
- 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.