Differential expression of immunohistochemical markers in primary lung and breast cancers enriched for triple-negative tumours

Histopathology. 2016 Feb;68(3):367-77. doi: 10.1111/his.12765. Epub 2015 Aug 7.

Abstract

Aims: In breast cancer patients presenting with a lung lesion, the distinction between lung and breast origin is clinically important. Lung and breast cancers are both CK7(+) /CK20(-) , so additional immunohistochemical markers are needed.

Methods and results: We examined the expression of oestrogen receptor (ER), progesterone receptor (PR), thyroid transcription factor-1 (TTF-1), gross cystic disease fluid protein-15 (GCDFP-15), p63 and Wilms' tumour 1 (WT1) in a series of tissue microarrays comprising 266 non-small-cell lung cancers and 837 primary breast cancers enriched for triple-negative tumours (TNBC). Staining for ER, PR, TTF-1 and GCDFP-15 was present in 63%, 49%, 0% and 25% of breast and 6%, 9%, 59% and 1% of lung cancers, respectively. Strong staining for p63 was present in 63 (97%) lung squamous cell carcinomas and only eight (9%) TNBC. WT1 nuclear staining was rare; however, cytoplasmic staining was identified in 49 (40%) TNBC and 10 (5%) lung cancers. Cluster analysis segregated TNBC from lung cancers with TTF-1 and/or p63 staining favouring lung origin, and GCDFP-15 or WT1 staining favouring breast origin. Cancers negative for all four markers (17%) were 60% breast and 40% lung origin.

Conclusion: An immunohistochemical panel incorporating ER, TTF-1, GCDFP-15, p63 and WT1 can help to distinguish lung cancer from metastatic breast cancer, including TNBC.

Keywords: breast cancer; immunohistochemistry; lung cancer; triple negative breast cancer.

MeSH terms

  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carrier Proteins / metabolism
  • Cluster Analysis
  • Diagnosis, Differential
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins
  • Nuclear Proteins / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • WT1 Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • CKAP4 protein, human
  • Carrier Proteins
  • Glycoproteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • NKX2-1 protein, human
  • Nuclear Proteins
  • PIP protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • WT1 Proteins
  • WT1 protein, human