ArticleAnnals of surgical oncology2020
MMR Deficiency is Homogeneous in Pancreatic Carcinoma and Associated with High Density of Cd8-Positive Lymphocytes.
Article in Annals of surgical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Personalised therapy in pancreatic carcinoma - a forthcoming opportunity?Przeglad gastroenterologiczny · 2026Review
- Genome-based classification of pancreatic acinar cell carcinoma reveals similarities to KRAS wild-type PDAC.Journal of translational medicine · 2025Article
- Dysfunctional mismatch repair in patients with early triple-negative breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- MTAP deficiency is highly homogeneous in advanced, muscle-invasive urothelial carcinoma of the urinary bladder.Scientific reports · 2025Article
- Clinical Implications of Mismatch Repair Deficiency in Pancreatic Ductal Adenocarcinoma.Cancer medicine · 2025Review
- Review
- The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine.Frontiers in immunology · 2023Review
- Diabetes mellitus impacts on expression of DNA mismatch repair protein PMS2 and tumor microenvironment in pancreatic ductal adenocarcinoma.Journal of diabetes investigation · 2023Article
- Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer.Frontiers in immunology · 2022Review
- Maintenance therapy of low-dose nivolumab, S-1, and leucovorin in metastatic pancreatic adenocarcinoma with a germline mutation ofFrontiers in immunology · 2022Article
- Immunotherapy in Combination with Well-Established Treatment Strategies in Pancreatic Cancer: Current Insights.Cancer management and research · 2022Review
- Intra-Tumoral CD8+ T-Cell Infiltration and PD-L1 Positivity in Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2022Article
- Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer.World journal of gastroenterology · 2021Review
- Colonic epithelial cathelicidin (LL-37) expression intensity is associated with progression of colorectal cancer and presence of CD8The journal of pathology. Clinical research · 2021Article
- Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development.Acta pharmaceutica Sinica. B · 2021Review
- DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness.PeerJ · 2021Article
- Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation.Clinical journal of gastroenterology · 2020Article
- Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma.International journal of immunopathology and pharmacologyArticle
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicrosatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in pancreatic cancer, but data on the possible extent of intratumoral heterogeneity are lacking.
methodsTo study MSI heterogeneity in pancreatic cancer, a tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6.
resultsIn six suspicious cases, large section immunohistochemistry and microsatellite analysis (Bethesda panel) resulted in the identification of 4 (0.8%) validated MSI cases out of 480 interpretable pancreatic ductal adenocarcinomas. MSI was absent in 55 adenocarcinomas of the ampulla of Vater and 7 acinar cell carcinomas. MMR deficiency always involved MSH6 loss, in three cases with additional loss of MSH2 expression. Three cancers were MSI-high and one case with isolated MSH6 loss was MSS in PCR analysis. The analysis of 44 cancer-containing tumor blocks revealed that the loss of MMR protein expression was always homogeneous in affected tumors. Automated digital image analysis of CD8 immunostaining demonstrated markedly higher CD8 + tumor infiltrating lymphocytes in tumors with (mean = 685, median = 626) than without (mean = 227; median = 124) MMR deficiency (p < 0.0001), suggesting a role of MSI for immune response.
conclusionsOur data suggest that MSI occurs early in a small subset of ductal adenocarcinomas of the pancreas and that immunohistochemical MMR analysis on limited biopsy or cytology material may be sufficient to estimate MMR status of the entire cancer mass.
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