Influence of anatomical subsite on the incidence of microsatellite instability, and KRAS and BRAF mutation rates in patients with colon carcinoma.
There is a growing amount of data supporting the concept that cancers originating from the proximal and distal colon are distinct clinicopathological entities. The incidence of MSI and BRAF mutation is strongly associated with right sided tumor location, whereas there are conflicting results for KRAS mutation rates. However, to date, no data exist whether and to what extent defined colonic subsites influence MSI status, KRAS and BRAF mutation rates. We selected primary colon cancer from 171 patients operated on at our institution between 2007 and 2010. BRAF, KRAS mutation rates and microsatellite instability were determined and correlated with clinicopathological features and tumor location. MSI-h cancers were significantly associated with poor histological grade but a lower rate of distant metastases. KRAS-mutated tumors were linked to lower T-stage and better differentiation. Colon carcinomas with BRAF mutation were significantly associated with distant metastatic spread and poor histological grade. Furthermore, we found that MSI-h status, KRAS and BRAF mutation rates varied remarkably among the colonic subsites irrespective of right- and left-sided origin, respectively. The results of the current study provide further evidence that a simple classification into right- and left-sided colon carcinoma does not represent the complexity of this tumor entity.
Department of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. frankbenedix@gmx.de
Frank
F
Benedix
Frank
F
Meyer
Rainer
R
Kube
Siegfried
S
Kropf
Doerthe
D
Kuester
Hans
H
Lippert
Albert
A
Roessner
Sabine
S
Krüger
D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins