title: Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses.
abstract: Mismatch 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 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.
  
  
  
  Patients with dMMR CRC identified by immunohistochemistry staining and 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, germ-line MMR mutation testing, and clinical course.
  
  
  
  A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 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; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis.
  
  
  
  CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.Genet Med 18 9, 863-868.
authors: Division of Medical Oncology, Department of Internal Medicine, Stanford University, Stanford, California, USA.
authors: Sigurdis
authors: S
authors: Haraldsdottir
authors: Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Heather
authors: 0000-0001-7558-9794
authors: H
authors: Hampel
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Christina
authors: C
authors: Wu
authors: Comprehensive Cancer Center, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Daniel Y
authors: DY
authors: Weng
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Peter G
authors: PG
authors: Shields
authors: Department of Pathology, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Wendy L
authors: WL
authors: Frankel
authors: Center for Biostatistics, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Xueliang
authors: X
authors: Pan
authors: Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.|Comprehensive Cancer Center, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.|Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Albert
authors: A
authors: de la Chapelle
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Richard M
authors: 0000-0003-3713-6895
authors: RM
authors: Goldberg
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA.
authors: Tanios
authors: T
authors: Bekaii-Saab
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: C501486:MLH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1