Evaluating mismatch repair deficiency in colorectal cancer biopsy specimens

• DOI: 10.1007/s00418-023-02202-8
• Publication Date: 2023-06-07T08:02:41Z
• Authors: F. Grillo; M. Paudice; A. Gambella; S. Bozzano; S. Sciallero; A. Puccini; S. Lastraioli; M. Dono; P. Parente; A. Vanoli; V. Angerilli; M. Fassan; L. Mastracci
• Keywords: MLH1; PMS2; Lynch Syndrome

Mismatch repair (MMR) testing on all new cases of colorectal cancer (CRC) has customarily been preferably performed surgical specimens, as more tissue is available; however, clinical trials for the use immune checkpoint inhibitors in neoadjuvant setting require MMR biopsy samples. This study aims at identifying advantages, disadvantages and any potential pitfalls evaluation how to cope with them. The prospective-retrospective, recruiting 141 biopsies (86 proficient (p)MMR 55 deficient (d)MMR) 97 paired specimens (48 pMMR; 49 dMMR). In a high number indeterminate stains was observed, particular MLH1 (31 cases, 56.4%). main reasons were punctate nuclear expression MLH1, relatively weak compared internal controls, or both (making loss difficult interpret), which solved by reducing primary incubation times MLH1. A mean ≥ 5 had adequate immunostains, ≤ 3 inadequate cases. Conversely, rarely suffered from reactions, while weaker staining intensity (p < 0.007) PMS2 increased patchiness grade 0.0001) seen. Central artefacts almost exclusive specimens. status classification possible 92/97 matched biopsy/resection specimen these concordant (47 pMMR 45 Evaluation CRC samples feasible, if interpretation are known, making laboratory-specific appropriate protocols fundamental high-quality diagnoses.