Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

被引:310
作者
Ward, R
Meagher, A
Tomlinson, I
O'Connor, T
Norrie, M
Wu, R
Hawkins, N
机构
[1] Imperial Canc Res Fund, London WC2A 3PX, England
[2] Univ New S Wales, Sch Pathol, Sydney, NSW 2052, Australia
[3] Univ New S Wales, Sch Med, Sydney, NSW 2052, Australia
[4] St Vincents Hosp, Dept Colorectal Surg, Darlinghurst, NSW 2010, Australia
[5] St Vincents Hosp, Dept Med Oncol, Darlinghurst, NSW 2010, Australia
关键词
colorectal carcinoma; microsatellite instability; survival; MLH1; MSH2; immunohistochemistry;
D O I
10.1136/gut.48.6.821
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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%) rumours 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.
引用
收藏
页码:821 / 829
页数:9
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