AIM: 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. CONCLUSION: 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.
AIM: To determine the prognostic significance of deficient mismatch repair (dMMR) and BRAFV600E in Thai sporadic colorectal cancer (CRC) patients. METHODS: We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRCpatients 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. BRAFV600E 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 BRAFV600E 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 dMMRtumors 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 BRAFV600E mutation had no prognostic impact on DFS and OS. CONCLUSION: The prevalence of dMMR and BRAFV600E in Thai sporadic CRCpatients was 15% and 11%, respectively. The dMMR phenotype was associated with a favorable outcome.
Entities:
Keywords:
BRAF; Mismatch repair; Overall survival; Sporadic colorectal cancer
Authors: Karin Fransén; Maria Klintenäs; Anna Osterström; Jan Dimberg; Hans-Jürg Monstein; Peter Söderkvist Journal: Carcinogenesis Date: 2003-12-19 Impact factor: 4.944
Authors: Guoren Deng; Ian Bell; Suzanne Crawley; James Gum; Jonathan P Terdiman; Brian A Allen; Brindusa Truta; Marvin H Sleisenger; Young S Kim Journal: Clin Cancer Res Date: 2004-01-01 Impact factor: 12.531
Authors: Harith Rajagopalan; Alberto Bardelli; Christoph Lengauer; Kenneth W Kinzler; Bert Vogelstein; Victor E Velculescu Journal: Nature Date: 2002-08-29 Impact factor: 49.962
Authors: Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal Journal: Nature Date: 2002-06-09 Impact factor: 49.962
Authors: João Cortez Pinto; Isadora Rosa; Catarina Martins; Inês Marques; João Pereira da Silva; Ricardo Fonseca; João Freire; António Dias Pereira Journal: J Gastrointest Cancer Date: 2020-03
Authors: George Kunnackal John; Vipin Das Villgran; Christine Caufield-Noll; Francis M Giardiello Journal: Fam Cancer Date: 2021-01-11 Impact factor: 2.375
Authors: George Kunnackal John; Vipin Das Villgran; Christine Caufield-Noll; Francis Giardiello Journal: Fam Cancer Date: 2020-09-11 Impact factor: 2.375
Authors: Cong-Min Zhang; Jin-Feng Lv; Liang Gong; Lin-Yu Yu; Xiao-Ping Chen; Hong-Hao Zhou; Lan Fan Journal: Int J Environ Res Public Health Date: 2016-09-08 Impact factor: 3.390
Authors: Jiao Yang; Xiang Lin Du; Shu Ting Li; Bi Yuan Wang; Yin Ying Wu; Zhe Ling Chen; Meng Lv; Yan Wei Shen; Xin Wang; Dan Feng Dong; Dan Li; Fan Wang; En Xiao Li; Min Yi; Jin Yang Journal: PLoS One Date: 2016-12-09 Impact factor: 3.240