Microsatellite instability in sporadic and inherited colon adenocarcinomas from Greek patients: correlation with several clinicopathological characteristics.
OBJECTIVE
Microsatellite instability seems to play a significant role in colorectal carcinogenesis, as it is reported to occur in HNPCC patients as well as in a proportion of sporadic cases. The aim of this study was to examine the presence of microsatellite instability in relation to other commonly observed genetic abnormalities and clinicopathological characteristics of sporadic and inherited colorectal cancers.


METHODS
One hundred and three sporadic colorectal adenocarcinomas and 9 adenocarcinomas from HNPCC patients were histologically evaluated. The presence of microsatellite instability was investigated at six loci. K-ras and p53 mutations, p53 LOH, hMLH1 expression and methylation status were examined as well. Statistical analysis was performed to define possible correlations of the observed genetic alterations with the clinicopathological characteristics of the analysed tumors.


RESULTS
High-grade microsatellite instability was found in 14% of sporadic adenocarcinomas and in 78% of adenocarcinomas from HNPCC patients. K-ras and p53 mutations were found in 29% and 28% of sporadic adenocarcinomas respectively and in 0% and 22% of the 9 HNPCC cases. A statistically significant correlation was noticed in sporadic tumors between the presence of MSI-H and tumor location at the proximal colon, as well as with the female gender.


CONCLUSIONS
Sporadic MSI+ colon adenocarcinomas seem to represent a distinct entity with a unique profile of genetic changes, different from those observed in HNPCC or MSI negative sporadic tumors.
Michalopoulos
N V
NV
Department of Pathology, Medical School, National and Kapodistrian University of Athens, Goudi, Athens, Greece.
Saetta
A A
AA
Lazaris
A C
AC
Gigelou
F
F
Koilakou
S
S
Patsouris
E
E
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005819:Genetic Markers; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000502:physiology*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005819:Genetic Markers; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1