Can evaluation of mismatch repair defect and TILs increase the number of triple-negative breast cancer patients eligible for immunotherapy?
| Autor: | Johanne Lade-Keller, Trine Tramm, Demet Özcan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
PD-L1
Oncology Adult medicine.medical_specialty medicine.medical_treatment Triple Negative Breast Neoplasms MLH1 DNA Mismatch Repair Tumor-infiltrating lymphocytes B7-H1 Antigen Pathology and Forensic Medicine Breast cancer Lymphocytes Tumor-Infiltrating Internal medicine PMS2 Biomarkers Tumor Medicine Humans Triple negative breast cancer Triple-negative breast cancer Aged business.industry Patient Selection Cell Biology Immunotherapy Middle Aged medicine.disease Immunohistochemistry digestive system diseases MSH6 DNA Repair Enzymes MSH2 Female business Mismatch repair deficiency |
| Zdroj: | Özcan, D, Lade-Keller, J & Tramm, T 2021, ' Can evaluation of mismatch repair defect and TILs increase the number of triple-negative breast cancer patients eligible for immunotherapy? ', Pathology Research and Practice, vol. 226, 153606 . https://doi.org/10.1016/j.prp.2021.153606 |
| ISSN: | 1618-0631 |
| Popis: | Background Programmed-cell-death-ligand 1 (PD-L1) inhibitor treatment is approved for metastatic/recurrent, PD-L1 positive, triple-negative breast cancer (TNBC) and solid tumors with mismatch repair (MMR) defect regardless of PD-L1 status. The analytical validity of PD-L1 has been questioned and adding evaluation of tumor-infiltrating lymphocytes (TILs) may identify patients likely to respond to immunotherapy. We investigated the association between MMR-deficiency and PD-L1 in TNBC; aiming to identify PD-L1 negative, TNBC patients that may be candidates for anti-PD-L1 immunotherapy. Methodology Paraffin-embedded tumor material from 44 TNBC patients was included. In 38 cases, immunohistochemical-staining´s on whole-slide sections were successful for all four MMR proteins (MSH2, MSH6, MLH1 and PMS2) and PD-L1 in 36 cases. MMR-status was categorized as positive (pMMR), heterogeneous (hMMR) or deficient (dMMR). Tumor-infiltrating lymphocytes (TILs) were evaluated on H&E sections. Results MMR stainings showed substantial intratumor heterogeneity. Four of 38 cases (11%) were recorded as dMMR with loss of ≥ 1 MMR-protein and 19 cases (50%) showed heterogeneous expression or partial loss (hMMR) of ≥ 1 MMR-protein. Three of 22 PD-L1 negative cases were dMMR (14%) and ten cases hMMR (45%). 16 of 22 PD-L1 negative cases (73%) showed high TILs. Conclusions A substantial proportion of PD-L1 negative, TNBC patients showed complete/partial loss of MMR and/or high TILs indicating that supplementing PD-L1 examination with these biomarkers may identify TNBC-patients that may be selected for immunotherapy. |
| Databáze: | OpenAIRE |
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