Evaluation of napsin A, TTF-1, p63, p40, and CK5/6 immunohistochemical stains in pulmonary neuroendocrine tumors

Am J Clin Pathol. 2014 Sep;142(3):320-4. doi: 10.1309/AJCPGA0IUA8BHQEZ.

Abstract

Objective: A panel of immunohistochemical (IHC) stains frequently used to subclassify non-small cell lung cancers (NSCLCs) includes napsin A, TTF-1, CK5/6, p40, and p63. The expression profiles of these stains in neuroendocrine tumors have not been systematically evaluated.

Method: Sixty-eight resected pulmonary neuroendocrine tumors, including 52 typical carcinoids (TCs), eight atypical carcinoids (ACs), seven small cell carcinomas (SCLCs) and one large cell neuroendocrine carcinoma (LCNEC), were stained for napsin A, TTF-1, p63, p40, and CK5/6. Tumors were scored as positive (>1% tumor cells reactive) or negative, and percentage of reactive tumor cells was recorded.

Results: Napsin A, p63, p40, and CK5/6 were consistently negative in neuroendocrine tumors. TTF-1 was positive in 17 of 52 TCs, 4 of 8 ACs, 5 of 7 SCLCs, and 0 of 1 LCNECs.

Conclusion: Pulmonary neuroendocrine tumors have a distinct but nonspecific profile on IHC panel commonly applied to subclassify NSCLCs. They are napsin A-/p40-/p63-/CK5/6-/TTF-1±. Recognizing this profile may have value in separating neuroendocrine tumors from NSCLCs.

Keywords: Carcinoid; Immunohistochemistry; Napsin A; Pulmonary neuroendocrine tumor.

MeSH terms

  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers, Tumor / metabolism*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Immunodominant Epitopes / metabolism
  • Immunohistochemistry
  • Keratin-5 / metabolism
  • Keratin-6 / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Membrane Proteins / metabolism
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Peptide Fragments / metabolism
  • Transcription Factors

Substances

  • Biomarkers, Tumor
  • CKAP4 protein, human
  • DNA-Binding Proteins
  • Immunodominant Epitopes
  • Keratin-5
  • Keratin-6
  • Membrane Proteins
  • P40, iodinated C-terminal peptide, human
  • Peptide Fragments
  • TTF1 protein, human
  • Transcription Factors
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human