Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

Ward, R., Meagher, A., Tomlinson, I., O'Connor, T., Norrie, M., Wu, R. and Hawkins, N. (2001) Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut, 48 6: 821-829. doi:10.1136/gut.48.6.821


Author Ward, R.
Meagher, A.
Tomlinson, I.
O'Connor, T.
Norrie, M.
Wu, R.
Hawkins, N.
Title Microsatellite instability and the clinicopathological features of sporadic colorectal cancer
Journal name Gut   Check publisher's open access policy
ISSN 0017-5749
Publication date 2001-06
Sub-type Article (original research)
DOI 10.1136/gut.48.6.821
Open Access Status Not Open Access
Volume 48
Issue 6
Start page 821
End page 829
Total pages 9
Place of publication London, United Kingdom
Publisher BMJ Group
Language eng
Formatted abstract
BACKGROUND AND AIMS 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.
Keyword Colorectal carcinoma
Immunohistochemistry
Microsatellite instability
MLH1
MSH2
Survival
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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