Evaluation ofKRAS,NRASandBRAFmutational status and microsatellite instability in early colorectal carcinomas invading thesubmucosa(pT1): towards an in-house molecular prognostication for pathologists?

Abstract

AimWe 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)).MethodsWe 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).ResultsKRAS 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).ConclusionAlthough 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.

Pathological Features and Prognostication in Colorectal Cancer

“…There is an association with poor differentiation, mucinous histology, and proximal location in the colon [ 55 , 56 , 65 ]. Its utility in prognostication varies according to stage, [ 56 , 66 , 67 ] and may be affected by the MSI status [ 60 , 61 , 62 , 63 ].…”

Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting

“…Generally, the most widely adopted procedure for MSI evaluation relies on the Sanger sequencing-based Bethesda panel, which covers two mononucleotide (BAT-25 and BAT-26) and three dinucleotide (D5S346, D2S123, and D17S250) repetitions [13] or, alternatively, a panel covering five poly-A mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-24, NR-27) [14]. However, recent studies have demonstrated that the fully automated PCR high-resolution melt curve analysis (Idylla TM , Biocartis, Mechelen, Belgium) [11,[15][16][17][18][19][20][21][22][23][24][25][26] and the automated microfluidic electrophoretic run chip-based assay (TapeStation 4200, Agilent Technologies, Santa Clara, CA, USA) are easier to use, faster, and less expensive than Sanger sequencing [11,27,28].…”

Tumour‐stroma ratio has poor prognostic value in nonpedunculated T1 colorectal cancer: A multicentre case‐cohort study

“…Interestingly, several studies have shown that similar to the TSR, other parameters known to be strongly prognostic in patients with advanced‐stage CRC (Immunoscore, CMS classification, MSS/MSI status, molecular testing of KRAS, BRAF and TP53 , etc.) were also of limited use in predicting prognosis in T1 CRC patients 20,30,31 . These results suggest that caution should be taken in extrapolating such prognosticators to this specific patient group, possibly due to several distinct biological characteristics of T1 CRCs.…”

“…were also of limited use in predicting prognosis in T1 CRC patients. 20,30,31 These results suggest that caution should be taken in extrapolating such prognosticators to this specific patient group, possibly due to several distinct biological characteristics of T1 CRCs. In order to improve risk stratification in T1 CRC patients, we suggest that T1 CRC-tailored prognosticators should be developed through translational studies in T1 CRCs.…”