Table 2

Advantages and limitations of the different methods for assessing MSI/dMMR status in pancreatic ductal adenocarcinoma

AdvantagesLimitations
Immunohistochemistry
 Widely available and reliable in PDAC using the staining for the four classical MMR proteins MLH1, PMS2, MSH2, MSH6 (above all for surgical specimens—‘large’ amount of tissue)Suboptimal tissue fixation may impact its reliability.
 EconomicalLimited by antibodies available.
 ReproducibleLimited by the amount of tissue. Limited/inadequate tissue can lead to false loss of MMR proteins in PDAC.
 Rapid turn-around timeCan give false results (eg, loss of expression of one MMR protein) in case of the presence of a different partner of MMR proteins in the usual MLH1-PMS2 and MSH2-MSH6 heterodimers (eg, MLH1-PMS1, MSH2-MSH3).
 More sensitive than MSI-PCR testing in detecting absence of MSH6
MSI-PCR
 ReproducibleNot able to detect the specific mutated gene.
 Can detect MSI/dMMR tumours that have intact
 MMR protein staining on IHC
Less sensitive than MSI-PCR testing in detecting absence of MSH6.
 Rapid turnaround time
NGS
 Reliable also in case of limited tissue/biopsy (also for EUS-FNB)Expensive.
 Can detect simultaneously specific somatic and germline mutations of different genesStill not widely available.
 Can also be used to assess MSI and TMBLonger turnaround time.
 Can identify targetable mutations
  • dMMR, defective mismatch repair; EUS-FNB, endoscopic ultrasound-guided fine-needle biopsy; IHC, immunohistochemistry; MMR, mismatch repair; MSI, microsatellite instability; NGS, next-generation sequencing; PDAC, pancreatic ductal adenocarcinoma; TMB, tumour mutational burden.