Connect Sign InMolecular testing in GI cancer
Molecular testing in gastrointestinal cancers has emerged as an exciting new field in pathology. In the gastrointestinal tract, this started with the work-up of Lynch syndrome. This work-up involves two major steps: determining whether a colorectal cancer is mismatch repair deficient, either by microsatellite instability or immunohistochemistry (IHC) for mismatch repair proteins, and then determining whether a mismatch repair deficient tumor is sporadic or Lynch syndrome-associated. Clues that a mismatch repair deficient tumor is sporadic are an IHC profile of loss of MLH1 and PMS2 combined with a BRAF V600E mutation and/or MLH1 promoter methylation. The second major application for molecular diagnostics in colorectal cancer involves determining the potential utility of cetuximab therapy directed against the EGFR receptor in advanced disease. In this case alterations in genes downstream of EGFR, including KRAS, NRAS, BRAF, PIK3CA and PTEN, render such treatment ineffective, and therefore evaluation of these downstream genes is important to insure that only patients who may benefit from a relatively toxic and expensive drug are treated. More molecular targets will undoubtedly be discovered in the future, greatly increasing the number of molecular diagnostic tests. This will make next generation sequencing, or massively parallel sequencing, a technique in which numerous genes are evaluated simultaneously, an increasingly attractive alternative to single gene tests, especially as the cost of next generation sequencing continues to decrease.
Dr. Samowitz is a medical director of solid tumor molecular diagnostics and histology, and a staff pathologist for the Anatomic Pathology Division at ARUP, as well as a professor of pathology at the University of Utah School of Medicine. He received his MD from SUNY Downstate, and completed residency training in anatomic pathology at the University of Chicago and fellowships in gastrointestinal pathology at Johns Hopkins Hospital. Specializing in gastrointestinal pathology and the molecular genetics of colorectal cancer, Dr. Samowitz is the medical director for numerous molecular tests in gastrointestinal cancer and other tumors, including microsatellite instability by IHC and PCR, mutational testing for BRAF, PIK3CA, and NRAS, evaluation for molar pregnancy, and specimen identification.
