An Institution-Wide Screening Program for Hereditary Non-Polyposis Colorectal Cancer Identified Microsatellite Instability in Patients Who Would Not Have Been Tested Using the Revised Bethesda Guidelines
Jaclyn L Jerz, Hidehiro Takei, Heather Hendrickson, Randall J Olsen, Mary R Schwartz. Methodist Hospital, Houston, TX
Background: Hereditary non-polyposis colorectal cancer (HNPCC, Lynch Syndrome) is characterized by a germ line mutation in DNA mismatch repair (MMR) genes. Traditionally, the Revised Bethesda Guidelines (RBG) have been used to select patients for HNPCC screening. However, the RBG may not be all inclusive. Thus, our hospital implemented a standardized microsatellite instability (MSI) testing protocol for all newly diagnosed colorectal cancers in patients under the age of 70 years.
Design: Laboratory and medical records were reviewed from patients representing the first consecutive 100 MSI tests performed. MSI, immunohistochemistry staining for mismatch repair proteins, and BRAF gene mutation data were evaluated.
Results: 49 men and 51 women with newly diagnosed colorectal cancer were screened. The average age was 51 years (range 22 to 87 years). A few patients over the age of 70 had MSI testing ordered. Cancers of all stages and anatomic locations were represented, including 11 cases of metastatic disease. Of note, only 15 cases were mucinous adenocarcinomas, a morphologic feature of HNPCC and criterion in the RBG. Microsatellite testing was abnormal (MSI-high) in 15 cases. All MSI-high tumors underwent follow-up testing for the BRAF mutation. Nine showed an actionable, “wild-type” BRAF result that would warrant further genetic testing. Although seven of these patients were over the age of 50, four had mucinous features, which would have triggered MSI testing by RBG. The remaining three patients would have been missed by strict adherence to the RBG.
Conclusions: A hospital-wide screening protocol for MSI has been successfully implemented at our institution. MSI-high tumors occurred at a frequency similar to previous publications. Importantly, three patients would not have been screened using the RBG. This is significant since patients with microsatellite instability are managed differently than those with sporadic carcinomas. Our initial data set indicates that the RBG for HNPCC microsatellite screening may be too stringent, specifically the age and histologic features criteria which are the criteria most readily available to the pathologist.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 99, Monday Morning