TY - JOUR
T1 - Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses
AU - Haraldsdottir, Sigurdis
AU - Hampel, Heather
AU - Wu, Christina
AU - Weng, Daniel Y.
AU - Shields, Peter G.
AU - Frankel, Wendy L.
AU - Pan, Xueliang
AU - De La Chapelle, Albert
AU - Goldberg, Richard M.
AU - Bekaii-Saab, Tanios
N1 - Publisher Copyright:
© 2016 American College of Medical Genetics and Genomics.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Purpose: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.Methods: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.Results: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.Conclusion:CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.
AB - Purpose: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.Methods: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.Results: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.Conclusion:CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.
KW - Lynch syndrome
KW - colorectal cancer
KW - deficient mismatch repair system
KW - hypermethylation
KW - survival
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U2 - 10.1038/gim.2015.184
DO - 10.1038/gim.2015.184
M3 - Article
C2 - 26866578
AN - SCOPUS:84984982048
SN - 1098-3600
VL - 18
SP - 863
EP - 868
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 9
ER -