Immunhistochemistry by means of widely agreed-upon markers (cytokeratins 5/6 and 7, p63, thyroid transcription factor-1, and vimentin) on small biopsies of non-small cell lung cancer effectively parallels the corresponding profiling and eventual diagnoses on surgical specimens

J Thorac Oncol. 2011 Jun;6(6):1039-49. doi: 10.1097/JTO.0b013e318211dd16.


Introduction: More detailed typing of non-small cell lung cancer on small biopsy specimens is increasingly required, albeit sometimes demanding with morphology alone. Little, however, is known about the likelihood of immunohistochemistry (IHC)-assessed small biopsies to effectively parallel profiling and, hence, eventual diagnoses of surgical specimens.

Methods: Sixty-three preoperative biopsies and the corresponding surgical specimens from 30 consecutive squamous cell carcinomas, 22 adenocarcinomas, 2 adenosquamous carcinomas, eight sarcomatoid carcinomas, and one yolk sac tumor were jointly evaluated semiquantitatively for cytokeratins 5/6 and 7, p63, thyroid transcription factor-1, and vimentin immunoreactivity. Surgical specimens were the gold standard for morphology and IHC.

Results: Hierarchic clustering analysis of both surgical specimens and biopsies showed a nonrandom and overlapping distribution of the relevant markers, which closely correlated with each other and the diverse tumor categories, as confirmed by mosaic plot analysis. There were no differences in area under the curve-receiver operating characteristic curves for each marker between any two samples, with the exception of p63 that paralleled more effectively squamous cell carcinoma on biopsies than surgical specimens. Fifty-nine of 63 (94%) lesions were correctly classified by IHC on biopsy compared with 53 of 63 (84%) by revised morphology, with the predictive positive value being 97% for squamous cell carcinoma, 88% for adenocarcinoma, and 100% for sarcomatoid and adenosquamous carcinoma. Yolk sac tumor and three of eight sarcomatoid carcinomas, however, failed any diagnostic recognition.

Conclusions: Diverse cell differentiation lineages of non-small cell lung cancer may be consistently detected by IHC in small biopsies, making the eventual typing of tumors effective in most cases.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Keratin-5 / analysis
  • Keratin-6 / analysis
  • Keratin-7 / analysis
  • Lung / chemistry
  • Lung / pathology*
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis
  • Reproducibility of Results
  • Thyroid Nuclear Factor 1
  • Transcription Factors / analysis
  • Tumor Suppressor Proteins / analysis
  • Vimentin / analysis


  • Biomarkers, Tumor
  • Keratin-5
  • Keratin-6
  • Keratin-7
  • NKX2-1 protein, human
  • Nuclear Proteins
  • TP63 protein, human
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Vimentin