Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer.
BACKGROUND
Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer.


METHODS
Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers.


RESULTS
Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P = 0.015).


CONCLUSIONS
Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.
Wright
C M
CM
Department of Surgery, Princess Alexandra Hospital, Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Research Foundation Clinical Research Centre, Brisbane, Queensland, Australia.
Dent
O F
OF
Barker
M
M
Newland
R C
RC
Chapuis
P H
PH
Bokey
E L
EL
Young
J P
JP
Leggett
B A
BA
Jass
J R
JR
Macdonald
G A
GA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016019:Survival Analysis