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Revised Bethesda guidelines effective at identifying patients at risk of colorectal cancer

The revised Bethesda guidelines, used for screening patients for a type of hereditary colorectal cancer, are effective for determining which patients should undergo further genetic testing, according to a study in the April 27 issue of JAMA.

Hereditary nonpolyposis colorectal cancer (HNPCC), also named Lynch syndrome, is a genetic disorder that accounts for approximately 1 percent to 3 percent of all colorectal cancers, according to background information in the article. HNPCC is caused by mutations in genes, mainly MSH2 and MLH1. In HNPCC, colorectal tumors have a DNA abnormality called microsatellite instability. Although a great advance in the understanding of the molecular basis of HNPCC has taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains challenging.

Virginia Pinol, M.D., of the University of Barcelona, Spain, and colleagues conducted a study to determine the most effective and efficient way to detect MSH2 or MLH1 gene carriers in patients with newly diagnosed colorectal cancers. The study included 1,222 patients from 20 hospitals in Spain with newly diagnosed colorectal cancer between November 1, 2000 and October 31, 2001. Patients underwent microsatellite instability testing and MSH2/MLH1 immunostaining (laboratory technique used to determine properties of tissue). Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline (cells that have genetic material that may be passed to a child) testing.

Two hundred eighty-seven patients (23.5 percent) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4 percent) had a mismatch repair deficiency. The researchers found that strategies based on either microsatellite instability testing or immunostaining patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8 percent and 81.8 percent; specificity, 98.0 percent and 98.2 perc
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Contact: Antoni Castells, M.D.
castells@clinic.ub.es
JAMA and Archives Journals
26-Apr-2005


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