Single-section assessment of DNA mismatch repair using PMS2/MSH6 double immunohistochemistry.

Authors

Yuichiro Hatano, Kohei Taniguchi, Akihiko Toji, Shinichi Terada, Hiroki Hamamoto, Tomohito Tanaka, Sang-Woong Lee, Yoshinobu Hirose

Published in

Human pathology. Pages 106215. Jul 18, 2026. Epub Jul 18, 2026.

Abstract

This retrospective diagnostic concordance study evaluated the feasibility and performance of PMS2/MSH6 double immunohistochemistry (DIHC) as a single-section screening tool for deficient mismatch repair (dMMR). The study was conducted at a single academic tertiary care center in Japan and included 1,025 consecutive Japanese patients surgically treated for de novo primary colorectal cancer (CRC) or endometrial cancer (EC) between 2018 and 2021, using tissue microarrays (TMA) rather than whole-slide sections. Following a two-step exclusion process-qualitative assessment of original surgical FFPE blocks (65 CRC and 41 EC cases) and of constructed TMA blocks (125 CRC)-794 cases (580 CRC and 214 EC) were analyzed using 2-mm-diameter TMA cores. The primary outcome was concordance of mismatch repair status between the DIHC index test and single immunohistochemistry (SIHC) as a reference standard, rather than a true gold standard, for MMR deficiency. DIHC identified dMMR in 6.7% of CRC and 22% of EC cases, and McNemar's test showed no significant difference in sensitivity between DIHC and SIHC. For MSI-H detection, assessed in a limited subset (N = 163), DIHC showed a sensitivity of 100% (95% CI: 67.6%-100%) and specificity of 98.1% (94.5%-99.5%). dMMR status by DIHC was significantly associated with right-sided location and medullary histology in CRC. Although rare, in three cases (0.4%), DIHC visualized heterogenous MSH6 loss within PMS2-deficient clones in a section. PMS2/MSH6 DIHC provides diagnostic performance comparable to conventional SIHC while conserving tissue and resources, suggesting potential utility for small biopsies and investigation of intratumoral MMR protein expression heterogeneity.

PMID:
42471063
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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