ArticleEndocrine pathology2020
Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas.
Article in Endocrine pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Research progress in diagnosis and treatment of pancreatic cancer with mismatch repair and microsatellite instability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- New Insights from the Expression of the Mismatch Repair System in Pituitary Neuroendocrine Tumors.Endocrine pathology · 2026Article
- Case Report: Apparent progressive complete mismatch repair protein loss during platinum-based chemotherapy in metastatic rectal neuroendocrine tumour grade 2.Frontiers in oncology · 2026Article
- MTAP deficiency is highly homogeneous in advanced, muscle-invasive urothelial carcinoma of the urinary bladder.Scientific reports · 2025Article
- Genomic and transcriptomic landscapes of metastatic neuroendocrine neoplasms from distinct primary sites and their clinical implications.Scientific reports · 2025Article
- Amphicrine carcinoma of the right colon, a report of a case and review of literature.Rare tumors · 2024Article
- Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
- Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.Cancer medicine · 2023Article
- The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.Cancers · 2022Review
- An update on the development of concepts, diagnostic criteria, and challenging issues for neuroendocrine neoplasms across different digestive organs.Virchows Archiv : an international journal of pathology · 2022Review
- Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective.Frontiers in oncology · 2022Review
- Management of Large Cell Neuroendocrine Carcinoma.Frontiers in oncology · 2021Review
- Long Survival and Prolonged Remission after Surgery and Chemotherapy in a Metastatic Mismatch Repair Deficient Pancreatic Neuroendocrine Carcinoma with MLH1/PMS2 Immunodeficiency and Minimal Microsatellite Shift.Endocrine pathology · 2020Article
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Authors and funding
19 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Neuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four cases suspicious for MSI were identified. Validation of MSI by repeated IHC on large sections and polymerase chain reaction (PCR)-based analysis using the "Bethesda Panel" confirmed MSI in 3 cecal NECs. One pancreatic NET G3 with MSI-compatible TMA results was MMR intact on large section IHC and microsatellite stable (MSS). The remaining 235 tumors exhibited intact MMR. Protein loss of MLH1/PMS2 was found in two and MSH6 loss in one cancer with MSI. Large section IHC on all available tumor-containing tissue blocks in NECs with MSI did not identify aberrant tumor areas with intact MMR. Our data indicate that MSI is common in colorectal NECs (3 out of 10) but highly infrequent in neuroendocrine neoplasms from many other sites. The lack of intratumoral heterogeneity of MMR deficiency suggests early development of MSI during tumorigenesis in a subset of colorectal NECs and indicates that microsatellite status obtained from small biopsies may be representative for the entire cancer mass.
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