Inter-observer variability in immunohistochemical assessment of mismatch repair proteins in colorectal cancer

Abstract

Aims Defective DNA mismatch repair (MMR) mechanisms occur in about 15% of colorectal cancers. Immunohistochemical detection of MMR protein expression is widely used as a screening tool to select patients for further genetic screening, and to predict response to chemotherapy in some patients; however, there are no universally agreed criteria for assessment of this staining. This study seeks to quantify inter-observer variability in assessment of these stains. Methods Nine histopathologists completed a questionnaire regarding their understanding of the MMR mechanisms and reporting criteria for these stains. Secondly, 50 cancers were stained for the MMR proteins MLH-1, MSH-2, MSH-6 and PMS-2. Four histopathologists, blinded to results of subsequent genetic studies, were asked to report the stains as they would normally do in routine practice. Results and Discussion There is significant variation between different pathologists, in terms of both their understanding of the MMR mechanism and their reporting criteria. Furthermore, in only 31/50 cases were there complete agreement between the four pathologists in the study, and the original report. This highlights the need for better defined criteria for assessing loss of expression of MMR proteins, and suggests that these stains may be better reported by specialists with a particular interest in this area.