MMR profile and microsatellite instability status in colorectal mucinous adenocarcinoma with synchronous metastasis: a new clue for the clinical practice

Aims Mucinous adenocarcinoma (MA) is associated with a high frequency of microsatellite instability (MSI). In the metastatic setting, it is crucial to establish mismatch repair (MMR) and/or MSI status. However, genetic heterogeneity between primary tumour and synchronous metastasis and the diagnostic accuracy of the assay may hamper the MMR/MSI status evaluation. Methods In this study, we assessed the concordance rate of the MMR/MSI status between primary tumour and paired synchronous metastasis of 25 MAs. MMR status was evaluated by immunohistochemistry (IHC), while MSI status was evaluated by using three different molecular approaches: microfluidic electrophoresis of PCR products (TapeStation 4200 platform), full-closed RTqPCR system (Idylla system) and multiplex amplification with fluorescent primers and subsequent DNA fragment analysis on an automated sequencer (Titano MSI test). Results The concordance rate between primary MA and metastasis was 21/21 (100%), 23/25 (92.0%), 23/25 (92.0%) and 21/25 (84%) by using IHC, Idylla system, Titano MSI test and TapeStation 4200 system. All the four methods used in our study displayed high concordant rate, ranging from 91.0% (IHC vs Tapestation 4200 platform) to 98.0% (IHC vs Titano). Conclusions Several methodologies are frequently adopted in routine practice to successfully perform MMR/MSI status analysis. The most relevant issues related to MMR/MSI status analysis in MAs concern with low percentage of neoplastic cell and abundant mucine that may affect the molecular analysis. Thus, it might be useful to acquire both primary and metastatic sample to evaluate the MMR/MSI status by integrating IHC evaluation and molecular methodologies to successfully perform molecular profiling for MA patients