Microsatellite instability in a population of sporadic colorectal cancers: correlation between genetic and pathological profiles.
BACKGROUND
Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear.


OBJECTIVE
To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours.


METHODS
Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed.


RESULTS
High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062).


CONCLUSIONS
These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.
Luceri
C
C
Department of Pharmacology, Institute of Pathology, University of Florence, Florence, Italy. cristina.luceri@unifi.it
De Filippo
C
C
Guglielmi
F
F
Caderni
G
G
Messerini
L
L
Biggeri
A
A
Mini
E
E
Tonelli
F
F
Cianchi
F
F
Dolara
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D017491:Genes, APC; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging