Mismatch repair protein expression in Amsterdam II criteria-positive patients in Taiwan.
BACKGROUND
Hereditary non-polyposis colorectal cancer (HNPCC) is characterized genetically by germline mutations in DNA mismatch repair (MMR) genes. Immunohistochemistry (IHC) has high sensitivity and specificity for identifying MMR-deficient tumours. This study investigated the clinical presentations and frequency of HNPCC in Taiwan by combined Amsterdam II criteria (AC-II) and IHC.


METHODS
In 1995-2003, 7108 patients with primary colorectal cancer registered in Chang Gung Memorial Hospital's Colorectal Cancer Registry were screened using AC-II. Tumour specimens were analysed for MMR protein expression by IHC, and relevant clinicopathological details were documented.


RESULTS
Some 83 patients fulfilled the AC-II. Clinicopathologically, 43 patients (52 per cent) had proximal tumours, ten (12 per cent) had poorly differentiated cancers, 17 (20 per cent) had mucinous adenocarcinoma and 51 (61 per cent) had stage I-II tumours. Seventeen patients developed second primary colonic and extracolonic cancers over a mean 7.2-year follow-up. Immunohistochemically, 58 patients were MMR protein deficient. They had a significantly earlier age of onset (P < 0.001), more proximal tumour location (P = 0.002), less advanced tumour stage (P = 0.008) and more second primary cancers (P = 0.017) compared with MMR-competent patients.


CONCLUSIONS
These data show significant differences in clinical features between MMR protein-deficient and MMR competent subgroups.
Chen
J R
JR
National Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
Chiang
J M
JM
Changchien
C R
CR
Chen
J S
JS
Tang
R P
RP
Wang
J Y
JY
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003111:Colonic Polyps / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015995:Prevalence; D013624:Taiwan / Q000453:epidemiology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes