ArticleVirchows Archiv : an international journal of pathology2026
Immunohistochemical profiling of small cell lung cancer reveals subtype heterogeneity and a tuft cell-like subtype characterized by LRMP and TRPM5.
Article in Virchows Archiv : an international journal of pathology, 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
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with marked molecular heterogeneity. Recent transcriptomic studies have identified a tuft cell-like SCLC subtype defined by POU2F3 expression, but its immunohistochemical features remain incompletely characterized. The aim of this study is to describe the immunohistochemical expression of the subtype-defining transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 in SCLC and to assess protein expression of tuft cell markers in the POU2F3-positive subset. We conducted an integrated analysis combining in silico evaluation of a published SCLC RNA-sequencing dataset with immunohistochemical profiling of 80 tumors. Protein expression of ASCL1, NEUROD1, POU2F3, YAP1, LRMP, and TRPM5 was quantified using H-scores, and associations were analyzed with chi-square or Fisher's exact tests. In silico analysis confirmed that SCLC-POU2F3 tumors exhibit a distinct tuft cell-like transcriptomic signature, with upregulation of tuft cell marker genes LRMP, TRPM5, AVIL, ASCL2, and COLCA2. IHC showed ASCL1, NEUROD1, POU2F3, and YAP1 expressions in 60%, 38%, 16%, and 6% of cases, respectively. Based on ASCL1/NEUROD1 expression patterns, cases were classified as ASCL1
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