ArticleFrontiers in oncology2026
Case Report: Apparent progressive complete mismatch repair protein loss during platinum-based chemotherapy in metastatic rectal neuroendocrine tumour grade 2.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Case presentation: 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 <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 <1 mut/Mb. Conclusions: 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.
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