Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses.

Abstract

PurposeMismatch repair deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of CRC cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups.MethodsPatients with dMMR CRC by immunohistochemistry staining treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients’ charts were accessed for information on pathology, germline MMR mutation testing and clinical course.ResultsA total of 143 patients had CRC associated with LS (37 pts, 26%) or MLH1-hm (106 pts, 74%). Patients with LS were younger, more often male, presented more often with stage III disease and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups while overall survival (OS) was longer in patients with LS but this difference was minimal after adjusting for age and stage at diagnosis.ConclusionCSS did not differ in LS-associated CRC compared to MLH1-hm CRC suggesting that they carry a similar prognosis.