Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors - PubMed (original) (raw)

Comparative Study

. 2003 Feb;162(2):469-77.

doi: 10.1016/S0002-9440(10)63841-2.

Patrick Franken, Jan Willem Dierssen, Wiljo De Leeuw, Juul Wijnen, Enno Dreef, Carli Tops, Martijn Breuning, Annette Bröcker-Vriends, Hans Vasen, Riccardo Fodde, Hans Morreau

Affiliations

Comparative Study

Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors

Yvonne Hendriks et al. Am J Pathol. 2003 Feb.

Abstract

Immunohistochemistry (IHC) of mismatch repair (MMR) proteins in colorectal tumors together with microsatellite analysis (MSI) can be helpful in identifying families eligible for mutation analysis. The aims were to determine sensitivity of IHC for MLH1, MSH2, and MSH6 and MSI analysis in tumors from known MMR gene mutation carriers; and to evaluate the use of tissue microarrays for IHC (IHC-TMA) of colon tumors in its ability to identify potential carriers of MMR gene mutations, and compare it with IHC on whole slides. IHC on whole slides was performed in colorectal tumors from 45 carriers of a germline mutation in one of the MMR genes. The TMA cohort consisted of 129 colon tumors from (suspected) hereditary nonpolyposis colorectal cancer (HNPCC) patients. Whole slide IHC analysis had a sensitivity of 89% in detecting MMR deficiency in carriers of a pathogenic MMR mutation. Sensitivity by MSI analysis was 93%. IHC can also be used to predict which gene is expected to harbor the mutation: for MLH1, MSH2, and MSH6, IHC on whole slides would have correctly predicted the mutation in 48%, 92%, and 75% of the cases, respectively. We propose a scheme for the diagnostic approach of families with (suspected) HNPCC. Comparison of the IHC results based on whole slides versus TMA, showed a concordance of 85%, 95%, and 75% for MLH, MSH2, and MSH6, respectively. This study therefore shows that IHC-TMA can be reliably used to simultaneously screen a large number of tumors from (suspected) HNPCC patients, at first in a research setting.

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Figures

Figure 1.

Figure 1.

Immunoreactivity in a TMA of mainly (suspected) HNPCC patients. A tissue core with a colon carcinoma from a patient with a germline hMLH1 missense mutation (1744C>T, L582F) is shown, stained for MLH1 (A), MSH2 (B), and MSH6 (C). MLH1 is abrogated, whereas MSH2 and MSH6 are present in the nuclei of the tumor cells. Slides were stained with antibodies against MLH1 (clone 14, Calbiochem, Cambridge, MA), MSH2 (clone GB12, Calbiochem), and MSH6 (clone 44, Transduction Laboratories/Becton Dickinson, Lexington, KY). Original magnifications, ×100.

Figure 2.

Figure 2.

Approach of patients with familial clustering of CRC. 1: IHC for MLH1, MSH2, MSH6, PMS2. 2: If the tumor is MSI-H, mutation analysis is the next step. 3: If the tumor is MSI-H and mutation has already been performed, research is the next step.

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