19. Correlation between loss of mismatch repair enzyme expression and microsatellite instability in colorectal carcinomas in a general hospital setting

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Aims To audit the correlation between immunostaining for DNA mismatch repair enzymes performed in routine diagnostic practice and the results of microsatellite instability analysis in colorectal carcinomas. Methods Immunostains for MLH1, MSH2, MSH6 and PMS2 were performed as part of the regular histopathological investigation of carcinomas of the large intestine. The microsatellite instability status was determined for all cases reported as showing loss of immunoexpression or equivocal immunoexpression. Results The study population consisted of 153 patients, of which 28 (18%) were classified as showing loss of immunoexpression, and 29 (19%) were classified as equivocal. All of the cases classified as showing loss of expression were microsatellite unstable. Of the 29 cases with equivocal expression, only one case was unstable on microsatellite analysis. Conclusions Loss of immunoexpression for mismatch repair enzymes can be reported reliably in a general hospital setting, and had a positive predictive value in this series of 100%. In our experience, an equivocal report on immunostaining was generally found in stable carcinomas. Microsatellite instability (MSI) is found in about 15% of colorectal carcinomas. In most cases, it is a sporadic phenomenon due to loss of expression of the enzyme MLH1 as a result of hypermethylation of the promoter region. Occasionally, it is due to a germline mutation in a gene encoding one of the DNA mismatch repair enzymes; such patients have Lynch syndrome, or hereditary non-polyposis colorectal cancer. Whether sporadic or hereditary, cancers with loss of DNA mismatch repair function exhibit a high level of instability in microsatellite regions of DNA and are described as unstable or showing high levels of MSI (MSI-H). To audit the correlation between immunostaining for DNA mismatch repair enzymes performed in routine diagnostic practice and the results of microsatellite instability analysis in colorectal carcinomas. Immunostains for MLH1, MSH2, MSH6 and PMS2 were performed as part of the regular histopathological investigation of carcinomas of the large intestine. The microsatellite instability status was determined for all cases reported as showing loss of immunoexpression or equivocal immunoexpression. The study population consisted of 153 patients, of which 28 (18%) were classified as showing loss of immunoexpression, and 29 (19%) were classified as equivocal. All of the cases classified as showing loss of expression were microsatellite unstable. Of the 29 cases with equivocal expression, only one case was unstable on microsatellite analysis. Loss of immunoexpression for mismatch repair enzymes can be reported reliably in a general hospital setting, and had a positive predictive value in this series of 100%. In our experience, an equivocal report on immunostaining was generally found in stable carcinomas.