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).
11 affiliations
- 1Faculty of Graduate Studies, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
- 2Department of Anatomy, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
- 3Department of Pathology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
- 4Department of Oncology, University Hospitals Plymouth NHS Trust, Plymouth, UK.
- 5Department of Community Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
- 6Department of Surgery, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
- 7National Hospital Kandy, Kandy, Sri Lanka.
- 8Department of Surgery, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
- 9Department of Paraclinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka.
- 10Gloucestershire Hospitals NHS Foundation Trust, Gloucestershire, UK.
- 11Department of Pathology/Centre for Cancer Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka. [email protected].
Abstract
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.
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BibTeX
@article{kosgallana2026novel,
title = {{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).}},
author = {Warunie Kosgallana and Sulochana Wijetunge and Sachini Malaviarachchi and Shamini Prathapan and Sanwari Hegoda and Kesara Ratnatunga and Palitha Ratnayake and Senaka Kandegedara and Bawantha Gamage and Iranthi Kumarasinghe and Siobhan Taylor and Isha Prematilleke},
journal = {BMC cancer},
year = {2026},
month = jul,
doi = {10.1186/s12885-026-16615-w},
url = {https://europepmc.org/article/MED/42958100},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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).
AU - Warunie Kosgallana
AU - Sulochana Wijetunge
AU - Sachini Malaviarachchi
AU - Shamini Prathapan
AU - Sanwari Hegoda
AU - Kesara Ratnatunga
AU - Palitha Ratnayake
AU - Senaka Kandegedara
AU - Bawantha Gamage
AU - Iranthi Kumarasinghe
AU - Siobhan Taylor
AU - Isha Prematilleke
PY - 2026
DA - 2026/07/31
JO - BMC cancer
DO - 10.1186/s12885-026-16615-w
UR - https://europepmc.org/article/MED/42958100
AB - 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.
SN - 1471-2407
ER -