Immunohistochemical analysis of lung carcinomas with pure or partial bronchioloalveolar differentiation

Arch Pathol Lab Med. 2004 Apr;128(4):406-14. doi: 10.1043/1543-2165(2004)128<406:IAOLCW>2.0.CO;2.


Context: In 1999, the World Health Organization redefined bronchioloalveolar carcinomas (BACs) as those neoplasms with only a pure lepidic growth pattern and no invasion.

Objectives: The present study examined 45 lung cancers with a BAC component (1) to determine whether these tumors would be classified as BACs by current World Health Organization standards, (2) to quantitate the BAC component within these tumors, and (3) to see if phenotypic differences exist between the so-called invasive and noninvasive regions of these tumors.

Design: Retrospective review of hematoxylin-eosin-stained slides and classification of histologic grade, tumor subtype, and percentage of pure BAC pattern, with further characterization by immunohistochemical staining for thyroid transcription factor 1, cytokeratin 7, cytokeratin 20, and Ki-67 antibodies.

Results: Only 7 (15.6%) of the 45 tumors examined could be classified as BAC by current strict World Health Organization criteria. Those tumors, classified as nonmucinous and mixed, showed similar immunohistochemical staining for cytokeratin 7, cytokeratin 20, and thyroid transcription factor 1; mucinous tumors showed disparate staining. Significant differences in immunohistochemical staining and tumor cell proliferation were seen for the regions of tumors designated as lepidic, infiltrative, and leading edge and for the regions of tumors with different histologic grades (ie, well, moderately, and poorly differentiated).

Conclusions: Nonmucinous and mixed BACs are phenotypically similar and show identical immunohistochemical staining patterns; mucinous tumors, on the other hand, show disparate immunohistochemical staining. Pulmonary neoplasms designated as adenocarcinomas with a BAC component represent a heterogenous group with a range of cell types, differentiation, growth, and immunophenotypes. Within an individual neoplasm, there are regional differences in these parameters as well.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar / chemistry
  • Adenocarcinoma, Bronchiolo-Alveolar / classification
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology*
  • Adenocarcinoma, Mucinous / chemistry
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Cell Differentiation
  • Connective Tissue / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Intermediate Filament Proteins / analysis
  • Keratin-20
  • Keratin-7
  • Keratins / analysis
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Nuclear Proteins / analysis
  • Phenotype
  • Retrospective Studies
  • Staining and Labeling
  • Thyroid Nuclear Factor 1
  • Transcription Factors / analysis


  • Biomarkers, Tumor
  • Intermediate Filament Proteins
  • KRT20 protein, human
  • KRT7 protein, human
  • Keratin-20
  • Keratin-7
  • NKX2-1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Keratins