title: Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer.
abstract: OBJECTIVE
  To determine the prognostic significance of deficient mismatch repair (dMMR) and BRAF V600E in Thai sporadic colorectal cancer (CRC) patients.
  
  
  METHODS
  We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1, 2006 and December 31, 2007 at Siriraj Hospital, Mahidol University. Formalin-fixed paraffin-embedded blocks of CRC tissue samples were analyzed for dMMR by detection of MMR protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction (PCR)-DHPLC. BRAF V600E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC. Associations between patient characteristics, MMR and BRAF status with disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox's proportional hazard regression.
  
  
  RESULTS
  dMMR and BRAF V600E mutations were identified in 31 of 208 (14.9%) and 23 of 211 (10.9%) tumors, respectively. dMMR was more commonly found in patients with primary colon tumors rather than rectal cancer (20.4% vs 7.6%, P =0.01), but there was no difference in MMR status between the right-sided and left-sided colon tumors (20.8% vs 34.6%, P = 0.24). dMMR was associated with early-stage rather than metastatic disease (17.3% vs 0%, P = 0.015). No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation. Six of 31 (19.3%) samples with dMMR carried the BRAF mutation, while 17 of 177 (9.6%) with proficient MMR (pMMR) harbored the mutation (P = 0.11). Notably, patients with dMMR tumors had significantly superior DFS (HR = 0.30, 95%CI: 0.15-0.77; P = 0.01) and OS (HR = 0.29, 95%CI: 0.10-0.84; P = 0.02) compared with patients with pMMR tumors. By contrast, the BRAF V600E mutation had no prognostic impact on DFS and OS.
  
  
  CONCLUSIONS
  The prevalence of dMMR and BRAF V600E in Thai sporadic CRC patients was 15% and 11%, respectively. The dMMR phenotype was associated with a favorable outcome.
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Krittiya
authors.initials: K
authors.lastname: Korphaisarn
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Ananya
authors.initials: A
authors.lastname: Pongpaibul
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Chanin
authors.initials: C
authors.lastname: Limwongse
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Ekkapong
authors.initials: E
authors.lastname: Roothumnong
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Wipawi
authors.initials: W
authors.lastname: Klaisuban
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Akarin
authors.initials: A
authors.lastname: Nimmannit
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Artit
authors.initials: A
authors.lastname: Jinawath
authors.affiliation: Krittiya Korphaisarn, Charuwan Akewanlop, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Charuwan
authors.initials: C
authors.lastname: Akewanlop
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Mismatch repair; Overall survival; Sporadic colorectal cancer