Microsatellite instability and the clinicopathological features of sporadic colorectal cancer.
OBJECTIVE
In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice.


METHODS
DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53.


RESULTS
Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%.


CONCLUSIONS
We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.
Ward
R
R
Department of Medical Oncology, St Vincent's Hospital, Victoria St, Darlinghurst, NSW, 2010, Australia. r.ward@garvan.unsw.edu.au
Meagher
A
A
Tomlinson
I
I
O'Connor
T
T
Norrie
M
M
Wu
R
R
Hawkins
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis