Year 2025 / Volume 117 / Number 2
Original
Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer

76-83

DOI: 10.17235/reed.2024.10645/2024

Carmen Martínez Lapiedra, Alfonso García-Fadrique, María Zaida García Casado, Samuel Navarro Fos, Isidro Machado Puerto,

Abstract
Microsatellite instability is found in 15% of sporadic colorectal cancers (CRC) and 95% of hereditary CRC cases. Lynch syndrome (LS) diagnosis begins with the analysis of the surgical specimen using methods such as immunohistochemistry (IHC), which identifies changes in the nuclear expression of DNA mismatch repair (MMR) proteins. However, IHC analysis on endoscopic biopsies could provide substantial benefits. Our goal was to assess the accuracy of MMR IHC status on endoscopic biopsies in comparison to corresponding surgical specimen in a series of CRC. We retrospectively selected patients who had undergone CRC surgery between February 2011 and January 2020 and had IHC testing for MMR proteins on the surgical specimen. The study was then performed on the corresponding endoscopic biopsies and results were compared. MMR IHC staining on surgical specimens were available for 361 CRC patients and only in 154 cases for preoperative endoscopic biopsies. The concordance between MMR IHC status of the endoscopic biopsy and the surgical specimen analysis was 98.6% for the MLH1/PMS2 proteins and 100% for MSH2/MSH6. In conclusion, endoscopic biopsies of colorectal tumors serve as a suitable tissue source for the immunohistochemical analysis of DNA repair proteins. The correlation with results from the surgical specimen was notably high and discrepancies were primarily as a result of intratumoral heterogeneity within the same sample. The features of MMR protein loss in endoscopic biopsies can provide clinicians with valuable information for specific therapeutic approaches and genetic counseling.
Lay Summary
Microsatellite instability, a genetic feature linked to colorectal cancer (CRC), is found in 15% of sporadic cases and 95% of hereditary cases, such as those with Lynch syndrome (LS). Diagnosing LS typically involves analyzing surgical tissue for changes in DNA mismatch repair (MMR) proteins using a technique called immunohistochemistry (IHC). However, this study explored whether IHC could be effectively performed on endoscopic biopsy samples. We compared the results of MMR IHC analysis from endoscopic biopsies with those from surgical specimens in 154 patients and found a high level of agreement—98.6% for the MLH1/PMS2 proteins and 100% for MSH2/MSH6—suggesting that endoscopic biopsies are reliable for detecting MMR protein loss. These findings could help clinicians make more informed treatment decisions and provide better genetic counseling.
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Martínez Lapiedra C, García-Fadrique A, García Casado M, Navarro Fos S, Machado Puerto I. Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer. 10645/2024


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Publication history

Received: 10/07/2024

Accepted: 09/10/2024

Online First: 18/10/2024

Published: 05/02/2025

Article revision time: 70 days

Article Online First time: 100 days

Article editing time: 210 days


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