BAI3, CDX2 and VIL1: a panel of three antibodies to distinguish small cell from large cell neuroendocrine lung carcinomas

Muhammad F Bari, Helen Brown, Andrew G Nicholson, Keith M Kerr, John R Gosney, William Wallace, Irshad Soomro, Salli Muller, Danielle Peat, Jonathan D Moore, Lesley A Ward, Maxim B Freidin, Eric Lim, Manu Vatish, David R J Snead

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Pages (from-to)547-56
Number of pages10
JournalHistopathology
Volume64
Issue number4
DOIs
Publication statusPublished - Mar 2014

Keywords

  • 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
  • Tumor Markers, Biological

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