Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis

J Thorac Oncol. 2010 Apr;5(4):436-41. doi: 10.1097/JTO.0b013e3181c6ed9b.


Introduction: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer.

Methods: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis.

Results: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype.

Conclusion: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Fine-Needle
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cytodiagnosis / methods
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Diagnosis, Differential
  • ErbB Receptors / genetics*
  • Genotype
  • Humans
  • Immunoenzyme Techniques
  • Keratin-5 / metabolism
  • Keratin-6 / metabolism
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mucins / metabolism*
  • Mutation / genetics
  • Neoplasm Staging
  • Nuclear Proteins / metabolism
  • Polymerase Chain Reaction
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Sensitivity and Specificity
  • Small Cell Lung Carcinoma / diagnosis
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / metabolism
  • Survival Rate
  • Thyroid Nuclear Factor 1
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / metabolism


  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Keratin-5
  • Keratin-6
  • Mucins
  • NKX2-1 protein, human
  • Nuclear Proteins
  • TP63 protein, human
  • Thyroid Nuclear Factor 1
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • EGFR protein, human
  • ErbB Receptors