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Background <p>Identifying dMMR (mismatch repair deficiency)/MSI (microsatellite instability) status in colorectal cancer (CRC) is standard in developed countries and is valuable for prognosis, management, and family screening. Universal testing is unfeasible in developing nations due to economic and resource constraints, limiting essential testing for optimal patient care. This study investigated the prevalence of dMMR/MSI CRC in Sri Lanka and introduced a predictive score for CRC patients in our population, which can be used to guide the selection of patients for cost-effective dMMR/MSI testing.</p> Methods <p>A cross-sectional analysis was conducted on colorectal carcinomas from Teaching Hospital Peradeniya, National Hospital Kandy, Colombo South Teaching Hospital, and General Sir John Kotelawala Defence University Hospital for two and a half years. Data collected included gender, age, tumour site, TNM stage, and family history of CRC. Haematoxylin and eosin-stained tumour slides of colectomy specimens were assessed for histopathological features. Immunohistochemistry (IHC) was performed for the four DNA mismatch repair proteins MLH1, MSH2, PMS2, and MSH6. Cases that were inconclusive by IHC were tested for MSI using PCR. Descriptive analysis included frequency, percentage, mean, standard deviation (SD) and range. Multivariable binomial logistic regression was conducted to select predictive variables.</p> Results <p>Of 185 patients, 104 (56.2%) were women. The mean age was 62.5 years (SD:11.8; range: 19–84). Of all cases, 23 (12.4%) were found to be mismatch repair deficient. Multivariable analysis showed significant association with age less than 60 years (<i>p</i> = 0.001), right sided tumour (<i>p</i> = 0.001), family history of CRC (at least one first or second degree relative) (<i>p</i> = 0.028), mucin percentage ≥ 20% (<i>p</i> = 0.038), solid region percentage ≥ 15% (<i>p</i> = 0.019), highest iTILs ≥ 3 per high power field (<i>p</i> &lt; 0.001), and Crohn-like peritumoral inflammation (<i>p</i> = 0.004). Considering the intercept values, rounded off to integers, a score was obtained for predicting dMMR/MSI CRC. The cutoff value for the prediction of dMMR status was taken as ≥ 6 from a maximum value of 20 (sensitivity: 0.957, specificity: 0.681).</p> Conclusions <p>In resource-limited settings, screening CRC patients with the proposed predictive score could cost-effectively guide dMMR/MSI testing. This preliminary score needs further validation in a larger independent cohort to ensure its reliability and broader applicability.</p>

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A novel predictive model for DNA mismatch repair deficient colorectal carcinoma for cost-effective MMR testing in low-resource settings: HERALD-MMR (Histological Evaluation and Risk Assessment using Local Demographics for Mismatch Repair)

  • 期刊论文

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  • 发表日期：

    2026年7月31日

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  • Warunie Kosgallana,
  • Sulochana Wijetunge,
  • Sachini Malaviarachchi,
  • Shamini Prathapan,
  • Sanwari Hegoda,
  • Kesara Ratnatunga,
  • Palitha Ratnayake,
  • Senaka Kandegedara,
  • Bawantha Gamage,
  • Iranthi Kumarasinghe,
  • Siobhan Taylor,
  • Isha Prematilleke

摘要

Background

Identifying dMMR (mismatch repair deficiency)/MSI (microsatellite instability) status in colorectal cancer (CRC) is standard in developed countries and is valuable for prognosis, management, and family screening. Universal testing is unfeasible in developing nations due to economic and resource constraints, limiting essential testing for optimal patient care. This study investigated the prevalence of dMMR/MSI CRC in Sri Lanka and introduced a predictive score for CRC patients in our population, which can be used to guide the selection of patients for cost-effective dMMR/MSI testing.

Methods

A cross-sectional analysis was conducted on colorectal carcinomas from Teaching Hospital Peradeniya, National Hospital Kandy, Colombo South Teaching Hospital, and General Sir John Kotelawala Defence University Hospital for two and a half years. Data collected included gender, age, tumour site, TNM stage, and family history of CRC. Haematoxylin and eosin-stained tumour slides of colectomy specimens were assessed for histopathological features. Immunohistochemistry (IHC) was performed for the four DNA mismatch repair proteins MLH1, MSH2, PMS2, and MSH6. Cases that were inconclusive by IHC were tested for MSI using PCR. Descriptive analysis included frequency, percentage, mean, standard deviation (SD) and range. Multivariable binomial logistic regression was conducted to select predictive variables.

Results

Of 185 patients, 104 (56.2%) were women. The mean age was 62.5 years (SD:11.8; range: 19–84). Of all cases, 23 (12.4%) were found to be mismatch repair deficient. Multivariable analysis showed significant association with age less than 60 years (p = 0.001), right sided tumour (p = 0.001), family history of CRC (at least one first or second degree relative) (p = 0.028), mucin percentage ≥ 20% (p = 0.038), solid region percentage ≥ 15% (p = 0.019), highest iTILs ≥ 3 per high power field (p < 0.001), and Crohn-like peritumoral inflammation (p = 0.004). Considering the intercept values, rounded off to integers, a score was obtained for predicting dMMR/MSI CRC. The cutoff value for the prediction of dMMR status was taken as ≥ 6 from a maximum value of 20 (sensitivity: 0.957, specificity: 0.681).

Conclusions

In resource-limited settings, screening CRC patients with the proposed predictive score could cost-effectively guide dMMR/MSI testing. This preliminary score needs further validation in a larger independent cohort to ensure its reliability and broader applicability.