Routine testing for mismatch repair deficiency in sporadic colorectal cancer is justified

Ward, Robyn Lynne, Turner, Jenny, Williams, Rachel, Pekarsky, Brita, Packham, Deborah, Velickovic, Marija, Meagher, Alan, O'Connor, Terence and Hawkins, Nicholas John (2005) Routine testing for mismatch repair deficiency in sporadic colorectal cancer is justified. Journal of Pathology, 207 4: 377-384. doi:10.1002/path.1851

Author Ward, Robyn Lynne
Turner, Jenny
Williams, Rachel
Pekarsky, Brita
Packham, Deborah
Velickovic, Marija
Meagher, Alan
O'Connor, Terence
Hawkins, Nicholas John
Title Routine testing for mismatch repair deficiency in sporadic colorectal cancer is justified
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 2005-12
Sub-type Article (original research)
DOI 10.1002/path.1851
Open Access Status Not yet assessed
Volume 207
Issue 4
Start page 377
End page 384
Total pages 8
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
Abstract This study prospectively examines the accuracy of immunohistochemical staining in the identification of mismatch repair defective (MMRD) colorectal cancer in routine clinical practice. The potential impact of this information on decisions regarding adjuvant treatment and germline testing were quantified. A consecutive series of fresh tissue (836 cancers) was obtained from 786 individuals undergoing curative surgery for colorectal cancer at one institution. As part of normal practice, each tumour was screened for the expression of MLH1 and MSH2 by immunohistochemical staining (IHC) and relevant clinicopathological details were documented. Microsatellite instability (MSI) was assessed using standard markers. Overall, 108 (13%) tumours showed loss of staining for either MLH1 (92 tumours) or MSH2 (16 tumours). The positive predictive value of mismatch repair IHC when used alone in the detection of MSI tumours was 88%, and the negative predictive value was 97%. Specificity and positive predictive value were improved by correlation with microsatellite status. Tumour stage (HR 3.5, 95% CI 2.0-6.0), vascular space invasion (HR 1.9, 95% CI 1.2-3.0) and mismatch repair deficiency (HR 0.2, 95% CI 0.05-0.87) were independent prognostic factors in stages II and III disease. Screening by mismatch repair IHC could reasonably have been expected to prevent ineffective treatment in 3.6% of stage II and 7.6% of stage III patients. The frequency of germline mismatch repair mutations was 0.8%, representing six unsuspected hereditary non-polyposis colorectal cancer (HNPCC) cases. Routine screening of colorectal cancers by mismatch repair IHC identifies individuals at low risk of relapse, and can prevent unnecessary adjuvant treatments in a significant number of individuals. Abnormal immunohistochemistry should be confirmed by microsatellite testing to ensure that false-positive results do not adversely impact on treatment decisions.
Keyword Chemotherapy
Colorectal cancer
Mismatch repair
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 32 times in Thomson Reuters Web of Science Article | Citations
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