Yield of Universal Testing for DNA Mismatch Repair Protein Deficiency in Colorectal Carcinoma From an Australian Community-based Practice

Abstract

AbstractLynch syndrome is the most common cause of inherited colorectal carcinoma (CRC). Testing all newly diagnosed CRC for MMR protein deficiency, known as universal testing, has recently emerged as the preferred approach to identify potential Lynch syndrome individuals. All newly diagnosed CRCs were screened for MMR protein expression by immunohistochemistry. A 2-step approach was used: PMS2 and MSH6 testing followed by the testing of the respective MMR protein partner if one of the proteins is lost. We retrospectively searched our pathology database for MMR protein expression results across a 5-year period (2012-2016) when universal testing was performed. Clinical and pathological data were extracted from the pathology report. A total of 2077 consecutive CRCs were tested for MMR protein expression. Mean age at diagnosis was 68.4 years. MMR protein deficiency was identified in 399 cases (19.2%). The vast majority of CRC with MLH1/PMS2 loss were diagnosed in patients older than 70 years (84%), most of them are likely to be secondary to sporadic MLH1 methylation. MMR protein deficiency patterns suggestive of a defect in MSH2, MSH6 or PMS2 comprised 42 cases, of which 37 were found in individuals aged 50 years or older. CRCs with MSH2/MSH6 loss were most commonly found in patients older than 70 years (57%). In summary, universal testing for MMR protein deficiency in CRC identifies abnormal patterns of expression suggestive of Lynch syndrome in all age groups. Further studies are needed to demonstrate the actual rate of Lynch syndrome individuals identified from this initial screening.