Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: A new approach to early lung cancer detection

M. S. Tockman, P. K. Gupta, J. D. Myers, J. K. Frost, S. B. Baylin, Ellen B Gold, A. M. Chase, P. H. Wilkinson, J. L. Mulshine

Research output: Contribution to journalArticle

192 Scopus citations

Abstract

Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small-cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men, ≥ 45 years of age, currently smoking ≥ 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (or greater) atypia. Sixty-nine of these (26 who progressed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of cancer. Subsequent specimens (average, 26 months before cancer) from participants who were originally considered 'false negative' did stain positively, improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clinical appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.

Original languageEnglish (US)
Pages (from-to)1685-1693
Number of pages9
JournalJournal of Clinical Oncology
Volume6
Issue number11
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Tockman, M. S., Gupta, P. K., Myers, J. D., Frost, J. K., Baylin, S. B., Gold, E. B., Chase, A. M., Wilkinson, P. H., & Mulshine, J. L. (1988). Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: A new approach to early lung cancer detection. Journal of Clinical Oncology, 6(11), 1685-1693.