Atypical adenomatous hyperplasia and adenocarcinoma of the human lung: their heterology in form and analogy in immunohistochemical characteristics

Cancer. 1996 Feb 15;77(4):665-74.


Background: In a previous study, morphometry and multivariate cluster analysis was performed on 97 lesions. These consisted of atypical adenomatous hyperplasia (AAH), considered to be an important lesion corresponding to a step of carcinogenesis for adenocarcinoma of the human lung, Clara cell type, and type 2 pneumocyte type adenocarcinomas. Although AAH and the two types of adenocarcinoma were re-classified into three clusters and AAH was defined in clear morphologic terms, the biologic nature of AAH has yet to be clarified. In the present study, immunohistochemical analysis was performed to gain a deeper understanding of the relationship between AAH and the two types of adenocarcinoma, and to compare the results with those obtained by morphometry.

Methods: The 97 lesions analyzed by morphometry were submitted to immunohistochemical analyses using antibodies against surfactant apoprotein A, urine protein 1, carcinoembryonic antigen and cytochrome P-450s (1A1-2, 2B1-2, 2E1). Also examined, as controls, were 17 lesions with adenomatous hyperplasia (AH), a non-neoplastic reactive change of bronchiolo-alveolar cells, 30 areas of normal Clara cells, and 36 areas of normal type 2 pneumocytes. The immunoreactivity was graded by introducing a semi-quantitative scoring system.

Results: Immunohistochemically, AAHs behaved quite similarly to the lesions classified as Clara cell type or type 2 pneumocyte type adenocarcinomas. For any of the antibodies employed, no significant difference in immunoreactivity was demonstrated among these lesions.

Conclusions: The results suggest, in accordance with our previous morphometry, that AAH is a lesion closely related with Clara cell type and type 2 pneumocyte type adenocarcinomas, probably as their common precursor. However, the two types of adenocarcinomas, despite their characteristic morphologic features, are indistinguishable using the biological indicators applied in this study.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenoma / pathology*
  • Analysis of Variance
  • Antibodies
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Apoproteins / analysis
  • Biomarkers
  • Biomarkers, Tumor / analysis*
  • Carcinoembryonic Antigen / analysis
  • Cluster Analysis
  • Cytochrome P-450 Enzyme System / analysis
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Lung / cytology
  • Lung / pathology*
  • Precancerous Conditions / pathology*
  • Proteins / analysis
  • Pulmonary Surfactant-Associated Proteins*
  • Pulmonary Surfactants / analysis
  • Reference Values
  • Retrospective Studies
  • Uteroglobin*


  • Antibodies
  • Antibodies, Monoclonal
  • Apoproteins
  • Biomarkers
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Proteins
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants
  • SCGB1A1 protein, human
  • pulmonary surfactant apoprotein
  • Cytochrome P-450 Enzyme System
  • Uteroglobin