ArticleFrontiers in medicine2026
Relationship between MLH1, MSH2, MSH6, and PMS2 protein expression status and clinicopathological characteristics in colorectal cancer tissues.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Deficient mismatch repair (dMMR) is a key molecular subtype of colorectal cancer (CRC) with significant prognostic and therapeutic implications, particularly regarding response to immunotherapy. The prevalence and clinicopathological features of dMMR CRC can vary by population. This research aimed to assess the prevalence of MMR protein deficiency and its relation to clinicopathological characteristics in Chinese CRC patients. Methods: Eighty patients with primary colorectal adenocarcinoma who underwent radical surgical resection were enrolled. Immunohistochemistry (IHC) was used to detect the expression of the four MMR proteins (MLH1, MSH2, MSH6, and PMS2). Patients were classified as dMMR or pMMR. Associations between MMR status and various clinicopathological features, including tumor location, differentiation, histology, and lymph node metastasis, were analyzed using Fisher's exact or chi-square tests, Spearman correlation, and simplified multivariable logistic regression with forward stepwise selection. Results: Of the 80 patients, 18 (22.5%) were identified as dMMR. The most common deficiency pattern was isolated PMS2 loss (50.0% of dMMR cases), followed by combined loss of MLH1/PMS2 (33.3%). Compared to the pMMR group, dMMR CRCs were significantly more likely to be located in the right colon (61.1% vs. 22.6%, Conclusion: The prevalence of dMMR in this cohort was 22.5%. dMMR CRCs display a distinct clinicopathological profile characterized by right-sided location, poor differentiation, mucinous histology, larger tumor size, along with a lower likelihood of lymph node metastasis. These findings support the value of routine IHC-based MMR testing in CRC patients. However, confirmatory molecular testing (e.g., MSI analysis, BRAF V600E mutation, MLH1 promoter methylation, or germline sequencing) is necessary to differentiate sporadic from Lynch syndrome-associated dMMR cases and to fully guide Lynch syndrome screening and immunotherapy decisions.
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