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. 2025 May 4;6(1):e70132.
doi: 10.1002/deo2.70132. eCollection 2026 Apr.

Endoscopic features of deficient mismatch repair/microsatellite instability-high and BRAF-mutated colorectal cancer

Affiliations

Endoscopic features of deficient mismatch repair/microsatellite instability-high and BRAF-mutated colorectal cancer

Rika Omote et al. DEN Open. .

Abstract

Objective: Recent advancements in genome analyses, including the BRAF gene and mismatch repair (MMR) gene/microsatellite instability (MSI), have revealed the biological diversity of colorectal cancer (CRC). BRAF-mutated CRC has a poor prognosis; however, cases exhibiting deficient MMR (dMMR)/MSI-high (MSI-H) and BRAF gene mutations have demonstrated significant prognostic improvement following recent immune checkpoint inhibitor therapy. Therefore, the diagnosis of these subtypes is important. This study aimed to identify the endoscopic features of dMMR/MSI-high and BRAF-mutated CRCs.

Methods: A retrospective analysis was conducted on 292 CRC cases. Clinicopathological findings, focusing on dMMR/MSI-H and BRAF-mutated subtypes, were determined. Endoscopic images were analyzed for the presence of yellow slough. Surface material characteristics were assessed through a histopathological evaluation.

Results: Of the 256 cases analyzed, 27 were dMMR/MSI-H CRC, including 12 BRAF-mutant cases. Yellow slough was observed in 83.3% of dMMR/MSI-H and BRAF-mutated CRCs, compared with 13.3% dMMR/MSI-H and BRAF wild-type CRCs and 1.3% pMMR/MSS and BRAF wild-type CRCs. Histological examination showed a correlation of yellow slough with coagulative necrosis and thicker surface layers in dMMR/MSI-high and BRAF-mutated CRCs.

Conclusion: Yellow slough on endoscopy may help identify dMMR/MSI-H- and BRAF-mutated CRC and allow the initiation of appropriate molecular testing and immunotherapy.

Keywords: BRAF; coagulative necrosis; colorectal cancer; dMMR/MSI‐high; yellow slough.

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Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
We classified cases into three categories: yellow slough (cases where a thick yellow adherent was observed on the surface of the colorectal tumor), white slough (cases where a white adherent was observed), and no slough (cases where no adherent or only mucus was observed).
FIGURE 2
FIGURE 2
Of the 294 cases, 36 were excluded due to reasons, such as specific types of cancer, lack of endoscopic images, inappropriate prior treatment, or severe stenosis. A total of 256 cases were included in the analysis. These cases were classified according to the results of RAS, RAF, and mismatch repair/microsatellite instability (MMR/MSI) examinations.
FIGURE 3
FIGURE 3
Yellow slough was observed in 83.3% of deficient mismatch repair/microsatellite instability‐high (dMMR/MSI‐high) and BRAF mt colorectal cancers. In contrast, it appeared in 13.3% of dMMR/MSI‐high and BRAF wt cases, 0% of pMMR/MSS/MSI‐low and BRAF mt cases, and 1.3% of pMMR/MSS/MSI‐low and BRAF wt cases.
FIGURE 4
FIGURE 4
Multivariate analysis showed BRAF mutation and deficient mismatch repair/microsatellite instability‐high (dMMR/MSI‐H) as independent risk factors. 95% confidence intervals for odds ratios on the logarithmic scale.
FIGURE 5
FIGURE 5
Endoscopic images of all 12 cases of deficient mismatch repair/microsatellite instability‐high and BRAF mt colorectal cancers. Ten of the 12 cases showed yellow slough. One case showed a white slough and the other showed a special endoscopic image similar to a submucosal tumor.
FIGURE 6
FIGURE 6
The surface adherent matter of the tumor was examined using the section with the deepest depth of invasion of the cancer in the surgical tissue. A thick necrotic layer was observed on the surface under low magnification, and under high magnification, the nuclei disappeared while maintaining the shape of the tumor. This was thought to be a coagulative necrosis image of the tumor.
FIGURE 7
FIGURE 7
The thickness of the tissue adhesion of surgical materials was analyzed in nine cases of yellow and 20 cases of white slough. The yellow slough was significantly thicker (4.0 vs. 0.8 mm, < 0.01).

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