An Unexpected Trend in the Prevalence of Microsatellite Instability in Colon Cancer
Brad D Barrows, Neda Zarrin-Khameh, Benjamin L Musher. Baylor College of Medicine, Houston, TX
Background: Lynch Syndrome (Hereditary Non-polyposis Colon Cancer) is an important cause of familial colon cancer with a reported prevalence of 10-15%. Paired mutations of DNA mismatch repair (MMR) genes are indirectly responsible for the development of neoplasia in Lynch Syndrome due to accumulation of mutations and microsatellite instability. The syndrome is inherited in an autosomal dominant pattern, although the tumors behave similar to a recessive disease due to the requirement of a somatic mutation to inactivate the uninvolved allele. The presence of MMR gene mutations is now reliably detected in tumor tissue by methods including immunohistochemistry and polymerase chain reaction (PCR) of MMR genes. Despite the reliability of current detection methods, additional investigation is required to better understand the natural progression and overall prevalence of this disease.
Design: To evaluate the prevalence of Lynch syndrome in our patient population, we performed a retrospective analysis of all colonic adenocarcinoma related surgical specimens collected at our General Hospital from 2009-2012. One hundred and fifty-one cases were identified and screened for mutation of MMR genes by immunohistochemistry.
Results: MMR gene mutation analysis showed a markedly reduced prevalence of confirmed Lynch syndrome, specifically in the African-American and Latino-American subgroups of our patient population (see table). The age range for the 8 cases showing positive MMR gene mutation was 33-66 years old with a mean age of 49. Tumors were predominantly found to arise in the ascending colon followed by transverse, descending, sigmoid and rectum (3, 2, 1, 1, 1 respectively).
|Colon cancer patient subpopulations||Number of patients||MMR gene mutation detected||MMR gene mutation absent||Prevalence|