ArticlePloS one2026
Performance of PREMM5, clinical criteria, and immunohistochemistry for MMR proteins in genetic risk assessment of Mexican patients with colorectal cancer.
Article in PloS one, 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
backgroundAll individuals with colorectal cancer (CRC) should undergo genetic cancer risk assessment given its implications for personalized treatment, surveillance, risk-reduction strategies, and cascade testing. Universal screening using immunohistochemistry (IHC) for mismatch repair (MMR) proteins in tumor tissue, when combined with clinical criteria, is essential for identifying individuals at higher risk for carrying germline pathogenic variants (PVs) in resource limited countries. PATIENTS AND
methodsThe spectrum of PVs in cancer susceptibility genes was characterized using NGS multigene panel assays among selected patients with CRC at two centers in Mexico. Germline genetic testing was used as the reference standard to evaluate the diagnostic accuracy of the referral criteria.
resultsFrom September 2018 to October 2024, 208 patients were enrolled. The median age at diagnosis was 45.0 years; 52.4% were women, 48.6% had deficient-MMR CRC, and 38.0% reported family history of CRC. Germline PVs were identified in 32.2% (n = 67); of these, 77.6% (n = 52) had Lynch syndrome (30 MLH1, 14 MSH2, 6 MSH6, and 2 PMS2), while 22.4% (n = 15) harbored PVs in other genes (4 ATM, 3 BRCA1, 3 CHEK2, 2 TP53, 1 BRCA2, 1 BRIP1, and 1 PALB2). Additionally, one individual harbored a monoallelic PV in MUTYH. The Amsterdam II criteria demonstrated the highest specificity (Sensitivity 56.0%, Specificity 91.9%), while the revised Bethesda criteria (Sensitivity 98.1%, Specificity 19.9%) and IHC for MMR proteins (Sensitivity 91.2%, Specificity 68.7%) exhibited high sensitivity. The area under the ROC curve for PREMM5 was 0.822 (95% CI 0.746-0.898).
conclusionPREMM5, Revised Bethesda criteria and IHC for MMR proteins effectively prioritized patients eligible for germline genetic testing in resource-limited settings. The performance of PREMM5 in this Mexican cohort was comparable to findings reported in validation studies within other populations. Considering the spectrum of PVs identified, employing a multigene panel test is recommended for Mexican patients with CRC.
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