High-frequency microsatellite instability and BRAF mutation (V600E) in unselected Serbian patients with colorectal cancer.
Microsatellite instability (MSI) is a genetic consequence of a MisMatch Repair defect in colorectal cancer (CRC). We compared clinicopathohistological features with MSI status of CRC and evaluated prognostic significance of MSI status and BRAF mutation in the group of MSI-H tumors. 155 primary CRCs were excised surgically, 2006-2008. MSI analysis was carried out using a fluorescence-based pentaplex polymerase chain reaction technique. BRAF mutation (V600E) was analyzed by direct sequencing in MSI-H tumors. For all patients were evaluated: age, gender, localization, tumor cell type, tumor differentiation, mucin production, lymphocytic infiltration (TILs) and TNM stage. Patients' disease-free survival (DFS) was compared according to MSI and BRAF status using Kaplan-Meier test. Of the 155 CRCs, 19 (12.3%) were MSI-H, and 136 (87.7%) were MSS/L. BRAF mutations were found in 4 of the MSI-H tumors. Patients with MSI-H CRC had lower recurrence rate (log rank test; P = 0.04) than MSS/L group. Patients with MSI-H tumor and BRAF mutation had worse DFS than MSI-H tumors without this mutation (log rank test; P = 0.01). Most of the clinicopathologic characteristics of MSI-H CRC in Serbian patients are similar to those reported in previous studies. Patients with MSI tumor phenotype had favourable prognosis, but in those with BRAF mutation higher recurrence rate was observed.
Center for Gastroenterology and Hepatology, Zvezdara University Clinical Center, Belgrade, Serbia. srdjanmarkovic@yahoo.com
Srdjan
S
Markovic
Jadranka
J
Antic
Neda
N
Dragicevic
Richard
R
Hamelin
Zoran
Z
Krivokapic
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf