{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:11Z","timestamp":1790575031202,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mismatch repair (MMR) deficiency is uncommon in gastroenteropancreatic neuroendocrine tumours (GEP-NETs), yet it represents a critical biomarker for immune checkpoint inhibitor (ICI) eligibility. Treatment-associated reduction or loss of MMR protein expression, often without corresponding MSI-H, has been reported in colorectal adenocarcinoma, but comparable changes have not been described in neuroendocrine tumours. Persistent discordance between immunohistochemistry (IHC)-based MMR protein assessment and next-generation sequencing (NGS)-based microsatellite instability (MSI) testing is an emerging and clinically challenging phenomenon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a 55-year-old woman initially diagnosed with rectal NET Grade 1 on endoscopic biopsy; the tumour was upgraded to NET Grade 2 (Ki-67 approximately 20%) on the surgical resectionk specimen. Hepatic metastases were confirmed four months after resection. The first liver biopsy (January 16, 2026) demonstrated partial MMR protein loss by IHC (MLH1-, MSH2+, MSH6-, PMS2-), while concurrent NGS showed microsatellite stability (MSS) and a tumour mutational burden (TMB) of &amp;lt;1 mut\/Mb. The patient received two cycles of surufatinib 250 mg orally once daily combined with intravenous carboplatin (500 mg, day 1) and etoposide (160 mg, days 1-3). Restaging CT demonstrated disease progression. A repeat liver biopsy (March 17, 2026) revealed complete loss of all four MMR proteins by IHC (MLH1-, MSH2-, MSH6-, PMS2-), while NGS again confirmed MSS and TMB &amp;lt;1 mut\/Mb.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To the best of our knowledge, this is the first reported case of apparent progressive complete MMR protein loss in the context of sequential platinum-based chemotherapy in metastatic rectal NET Grade 2, with persistent IHC-NGS discordance throughout. These findings raise an important question regarding how IHC-defined dMMR should be interpreted in the absence of NGS-confirmed MSI-H, and highlight the complexity of immunotherapy eligibility decisions in rare tumour types. Prospective data are needed to guide clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1885566","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:25Z","timestamp":1790574265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Apparent progressive complete mismatch repair protein loss during platinum-based chemotherapy in metastatic rectal neuroendocrine tumour grade 2"],"prefix":"10.3389","volume":"16","author":[{"given":"Yue","family":"Yang","sequence":"first","affiliation":[{"name":"Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Li","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Wang","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Wu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxin","family":"Tang","sequence":"additional","affiliation":[{"name":"Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]},{"name":"First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang","place":["Guizhou, China"]},{"name":"Affiliated Hospital of Zunyi Medical University, Zunyi","place":["Guizhou, 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