With recent advances in molecular diagnostic methods and targeted
cancer therapies, several molecular tests have been recommended for
gastric cancer (GC) and
colorectal cancer (CRC).
Microsatellite instability analysis of
gastrointestinal cancers is performed to screen for
Lynch syndrome, predict favorable prognosis, and screen patients for
immunotherapy. The
epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor has been approved in metastatic
CRCs with wildtype RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of
human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable
CRCs, and thus is helpful for ruling out
Lynch syndrome. In addition, the KRAS mutation is a prognostic
biomarker and the PIK3CA mutation is a molecular
biomarker predicting response to
phosphoinositide 3-kinase/AKT/
mammalian target of rapamycin inhibitors and response to
aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2
silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus-positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.