Taiwan hospital-based detection of Lynch syndrome distinguishes 2 types of microsatellite instabilities in colorectal cancers.
BACKGROUND
With progress in techniques of molecular biology, the phenotypes and genotypes for Lynch syndrome are more diverse than thought previously. This hospital-based study estimated the incidence and molecular and clinicopathologic features of Lynch syndrome to modify the screening criteria for Taiwanese patients with colorectal cancer (CRC).


METHODS
A total of 561 CRC patients were enrolled. DNA was extracted from neoplasms, normal mucosa, and/or white blood cells for analyses of microsatellite instability (MSI), BRAF mutation, MLH1 methylation, and sequencing of MMR genes. Immunohistochemistry (IHC) staining for MMR proteins was done for cases that fulfilled revised Bethesda criteria and for high-frequency microsatellite instability (MSI-H) neoplasms.


RESULTS
There were 136 (24.2%) and 10 (1.8%) cases that fulfilled the Revised Bethesda and Amsterdam II criteria (ACII), respectively. MSI-H was detected in 41 (7.3%), of which 32 showed abnormalities for > or = 1 MMR protein by IHC; low-frequency MSI (MSI-L) or microsatellite stable showed abnormal MSH2 staining in only 1 of 117 neoplasms. Thirteen (2.3%) cases had mutations in MMR genes with MLH1 (n = 10), MSH2 (n = 2), or MSH6 (n = 1). Of 13 Lynch syndrome cases, 3 (23.1%) and 11 (84.6%) fulfilled ACII and revised Bethesda criteria, respectively; 12 cases (93.3%) were MSI-H, and all had expression loss of > or = 1 MMR protein. Eight patients were >50 years old, 2 of whom did not fulfill revised Bethesda criteria. For MSI-H neoplasms without definite mutations, 72.4% and 44.8% showed MLH1 methylation and a BRAF (V599E) mutation, respectively. Lynch-associated CRC and sporadic MSI neoplasms shared similar clinicopathologic features.


CONCLUSIONS
In Taiwan, the incidence of Lynch syndrome was 2.3% among the 561 CRC patients evaluated. For Taiwanese CRC patients who are younger than age 60 whether or not fulfilling the Bethesda criteria should receive MSI or IHC screening for identification of the Lynch syndrome.
Chang
Shih-Ching
SC
Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, No 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan.
Lin
Pei-Ching
PC
Yang
Shung-Haur
SH
Wang
Huann-Sheng
HS
Liang
Wen-Yih
WY
Lin
Jen-Kou
JK
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D006769:Hospitals, General; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein