Do MSI-L sporadic colorectal tumors develop through "mild mutator pathway"?
BACKGROUND
The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain. The objective of this study was to further clarify if the MSI-L phenotype could reflect a distinct pathway of tumor development with a different clinical behavior.


METHODS
We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors.


RESULTS
We have found that MSI-L tumors are someway in the middle of MSI-H and MSS CRC, as they share some features with each of the other 2 subgroups: left side location, lower incidence of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L tumors show higher incidence of KRAS mutations.


CONCLUSIONS
We believe that MSI-L tumors could be considered a distinct phenotype that develops through a "mild mutator pathway."
Oliart
Soledad
S
Servicio de Cirugía, Hospital Central de la Cruz Roja San José y Santa Adela, Reina Victoria, Madrid, Spain.
Martínez-Santos
Cristina
C
Moreno-Azcoita
Mariano
M
Cerquella
Carlos
C
Nejda
Nargisse
N
Daimiel
Lydia
L
Iglesias
Daniel
D
Fernández-Peralta
Antonia M
AM
González-Aguilera
Juan J
JJ
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D018631:ras Proteins
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins