RESPONSE: Re: Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability

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Dr. Laghi proposes that all colorectal cancers be screened for microsatellite instability (MSI) using BAT26 as a marker rather than selecting patients based on family history for screening with the National Cancer Institute (NCI) panel of markers, as proposed in the revised Bethesda Guidelines (Table 1 ) ( 1 ) . This issue—that using just one MSI marker might make analysis simple and relatively inexpensive and hence would allow all patients with colorectal cancers to be screened, regardless of recommended screening guidelines—has been discussed before ( 2 ), and it needs careful examination, similar to what it received during the adoption of the NCI panel of markers. Most of the clinical and translational research experts did not feel that use of a single marker, even after applying screening guidelines, would identify the true number of hereditary nonpolyposis colorectal cancer (HNPCC) cases. In this Workshop, it was recognized that although markers like BAT26 are effective at determining MSI, they are not 100% sensitive (no false-negatives) or 100% specific (no false-positives), as suggested by Dr. Laghi. For example, BAT26 revealed MSI in 73 of 494 colorectal cancer patients, but when five markers were used, the number of patients with MSI increased to 95 of 494 ( 3 ) . Similarly, of 20 ovarian cancers with confirmed MSI, only five showed BAT26 instability ( 4 ), confirming results found in the literature for ovarian and endometrial cancers.