Molecular Testing for Gastrointestinal Cancer.

Lee HS1,2, Kim WH2, Kwak Y1,2, Koh J2, Bae JM3, Kim KM4, Chang MS2,3, Han HS5, Kim JM6, Kim HW7, Chang HK8, Choi YH9, Park JY10, Gu MJ11, Lhee MJ12, Kim JY13, Kim HS14, Cho MY15; Gastrointestinal Pathology Study Group of Korean Society of Pathologists; Molecular Pathology Study Group of Korean Society of Pathologists.

Author information

Abstract

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.

KEYWORDS:

Colorectal neoplasms; Gastric neoplasms; Molecular diagnosis; Prognosis; Targeted therapy

PMID:: 28219002
PMCID:: PMC5357760
DOI:: 10.4132/jptm.2017.01.24

Free PMC Article

From HuGE Literature Finder Database

This database contains published literature on genetic associations and other human genome epidemiology

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