KRAS, NRAS, BRAF mutations and high counts of poorly differentiated clusters of neoplastic cells in colorectal cancer: observational analysis of 175 cases.
A novel grading system based on the counting of poorly differentiated clusters (PDC) of neoplastic cells at the invasive margin and in the tumour stroma was recently introduced among the histological parameters predictive of adverse clinical outcome in colorectal cancer (CRC). The aim of this study was to correlate the histological grade based on PDC and the mutational status of KRAS, NRAS and BRAF genes in 175 consecutive CRCs. The highest PDC count under the objective lens of a ×20 microscopic field in each tumour was considered for grading assessment, so that PDC counts <5, 5-9 and ≥10 PDCs were defined grade 1, grade 2 and grade 3, respectively. Hotspots mutations were identified using the MassArray platform. Overall, there were 42 (24%) mutated tumours. Mutational status was significantly associated with high pT stage (p = 0.0021), advanced pTNM stage (p = 0.0018), nodal metastases (p = 0.006), tumour budding (p = 0.022) and high PDC grade (p = 0.0022). KRAS mutations were significantly associated with PDC grade (p = 0.0379), while BRAF mutations were associated with PDC-G3 although statistical significance was not reached. No significant associations were found between NRAS and PDC. The significant association between mutated KRAS and PDC grade suggests that KRAS mutations may be involved in the formation of PDC.
1Department of Human Pathology, University of Messina, Messina 2Department of Pathological Anatomy, University of Modena and Reggio Emilia, Modena, Italy.
Valeria
V
Barresi
Luca Reggiani
LR
Bonetti
Stefania
S
Bettelli
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D060787:Neoplasm Grading / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)