The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer genetic testing remains a critical issue.
The Bethesda guidelines were developed to preselect patients for microsatellite instability testing before germline mutation screening.
These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed.
Dr Catherine Julié and colleagues from France evaluated the performance of these revised guidelines for identifying patients with hereditary nonpolyposis colorectal cancer in a series of unselected consecutive patients.
The research team compared this revised guidelines-based approach with a molecular strategy.
The team evaluated 214 patients with newly diagnosed colorectal cancer.
|10% had microsatellite instability-positive tumors|
|The American Journal of Gastroenterology |
The microsatellite instability analysis was performed for all tumors.
The team performed germline testing, guided by immunohistochemical staining for mismatch repair proteins, and for patients with microsatellite instability-positive tumors.
Sporadic microsatellite instability-positive tumors were identified by screening for BRAF mutation and MLH1 promoter methylation.
The researchers found that 90 patients met the revised guidelines.
The team noted that 10% of patients had microsatellite instability-positive tumors.
Germline testing identified 8 mutations.
The team observed that the revised guidelines failed to identify 2 of the 8 probands.
In contrast, the molecular strategy identified all patients requiring testing for germline mutation.
The percentages of patients selected for germline testing by the revised guidelines, and the molecular strategy were 4% and 5%, respectively.
Dr Julié’s team concluded, “The revised Bethesda guidelines did not identify all hereditary nonpolyposis colorectal cancer cases in our series.”
“The molecular approach identified all hereditary nonpolyposis colorectal cancer patients with microsatellite instability -positive tumors, increasing the workload for germline testing only slightly.”