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AIMS: Discriminating small-cell lung carcinoma (SCLC) from large-cell neuroendocrine carcinoma (LCNEC) rests on morphological criteria, and reproducibility has been shown to be poor. We aimed to identify immunohistochemical markers to assist this diagnosis. METHODS AND RESULTS: Gene expression profiling on laser captured frozen tumour samples from eight SCLC and eight LCNEC tumours identified a total of 888 differentially expressed genes (DEGs), 23 of which were validated by qRT-PCR. Antibodies to four selected gene products were then evaluated as immunohistochemical markers on a cohort of 173 formalin-fixed paraffin-embedded (FFPE) SCLC/LCNEC tumour samples, including 26 indeterminate tumours without a consensus diagnosis. Three markers, CDX2, VIL1 and BAI3, gave significantly different results in the two tumour types (P < 0.0001): CDX2 and VIL1 in combination (either marker positive) showed sensitivity and specificity of 81% for LCNEC while BAI3 showed 89% sensitivity and 75% specificity for SCLC. Of the 26 indeterminate tumours 15 (58%) showed an immunophenotype suggesting either SCLC or LCNEC, eight (31%) showed staining of both tumour types, and three (11%) were negative for all markers. CONCLUSION: A panel of three markers, BAI3, CDX2 and VIL1, is a useful adjunct in the diagnosis of these tumour types.

Original publication




Journal article



Publication Date





547 - 556


BAI3, CDX2, VIL1, biomarkers, gene expression profiling, immunohistochemistry, large-cell neuroendocrine lung carcinoma, small-cell lung carcinoma, Biomarkers, Tumor, CDX2 Transcription Factor, Carcinoma, Neuroendocrine, Carcinoma, Small Cell, Cohort Studies, Diagnosis, Differential, Gene Expression Profiling, Homeodomain Proteins, Humans, Immunohistochemistry, Laser Capture Microdissection, Lung Neoplasms, Microfilament Proteins, Nerve Tissue Proteins, Reverse Transcriptase Polymerase Chain Reaction