Aim: Lynch syndrome is an inherited cancer syndrome associated with an increased lifetime risk of colorectal cancer (CRC) and characterized by germline mutations to one of four DNA mismatch repair (MMR) genes. Immunohistochemical (IHC) testing is used to screen for Lynch syndrome; however, despite routine completion following resection of primary CRC, it is only variably completed following resection of recurrent disease. This may be significant, as MMR protein expression can change from primary to recurrent CRC. The primary aim of this study is to investigate how MMR profiles change from primary to recurrent CRC; the secondary aim is to assess rates of MMR testing of primary and recurrent disease.
Method: We conducted a retrospective analysis of patients undergoing surgery for recurrent CRC from 2018-19 at a high-volume institution. MMR profiles were obtained following both primary and recurrent resection of CRC, and MMR protein expression was evaluated from both time points.
Results: A total of 107 patients met the inclusion criteria and IHC results were obtained for both primary and recurrent resections in 85 cases. MMR profiles changed in nine patients (10.6%), with a loss of staining from primary to recurrent disease in six (7.1%) and a gain of staining in three (3.5%). IHC testing was completed following 88.7% of primary and 39.3% of recurrent resections.
Conclusion: MMR profiles can change from primary to recurrent CRC and repeat MMR testing for recurrent CRC is completed in only a minority of cases.
Keywords: DNA mismatch repair; Lynch syndrome; colorectal cancer; immunohistochemistry; recurrent colorectal cancer.
© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.