Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair
BACKGROUND Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS To assess the feasibility of using immunohistochemistry to detect replication error...
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Published in | Gut Vol. 45; no. 3; pp. 409 - 415 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd and British Society of Gastroenterology
01.09.1999
BMJ BMJ Publishing Group LTD |
Subjects | |
Online Access | Get full text |
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Summary: | BACKGROUND Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens. |
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Bibliography: | Dr L Cawkwell, Molecular Oncology, Algernon Firth Institute of Pathology, School of Medicine, University of Leeds, Leeds LS2 9JT, UK. local:gutjnl;45/3/409 ark:/67375/NVC-NK7286ZG-0 href:gutjnl-45-409.pdf istex:5AACF01DCE6AC1C14C6B4DB0D0D926FAFBE200A3 PMID:10446111 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0017-5749 1468-3288 1458-3288 |
DOI: | 10.1136/gut.45.3.409 |