Prospective trial evaluating immunocytochemical-based sputum techniques for early lung cancer detection: Assays for promotion factors in the bronchial lavage

F. Scott, F. Cuttitta, A. M. Treston, I. Avis, P. Gupta, J. Ruckdeschel, Karen Kelly, S. Piantadosi, M. Tockman, J. Mulshine

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

To confirm the results of a previous report on the use of monoclonal antibodies in immunocytochemical assays of sputums for the early detection of lung cancer, we designed a new prospective trial in an independent clinical trial population. Since well-characterized Stage I resected non-small cell lung cancer patients have a low rate of tumor relapse and a high (1-3%/year) chance of developing a second primary lung cancer, they comprise a very favorable group for conducting an early lung cancer detection trial. The rate of new lung cancer is about 10-fold in excess of a standard 'high' risk population of smokers. To optimize the chance for a favorable outcome, all of the technical components for the trial have been systematically evaluated to ensure that optimal procedures are employed. For example, automated immunostaining of the sputum specimens will be performed. Bronchial lavages will be analyzed in a subset of the trial participants to define additional targets for early lung cancer detection. Two markers will be quantitated, including gastrin releasing peptide and peptidyl glycine α-amidating monooxygenase activity. These two markers assess the epithelium's capacity to produce growth factors which may be central to the biology of tumor promotion. Since these assays have not been performed in this context before, we attempted to optimize the specimen handling to permit the receipt of the material from a range of collaborating clinical sites in a condition that permits accurate quantitation of these two biomarkers. Efforts to standardize the assay endpoint stimulated the development of computer-assisted methods of immunocytochemical analysis. An algorithm for image analysis was developed as a result of systematic analysis of a range of potentially quantifiable assay endpoints with a panel of teaching cases. When a sampling of the original immunostained material from the first monoclonal antibody-based early lung cancer detection report was reanalyzed using the image analysis algorithm, a 90% concurrence with the original immunostaining interpretation was observed. These results suggest that there was an objective basis to the first report and that image analysis can greatly refine the process of early lung cancer detection research. An update of the current trial status will be summarized emphasizing the unique challenges presented in early cancer detection research.

Original languageEnglish (US)
Pages (from-to)175-183
Number of pages9
JournalJournal of Cellular Biochemistry
Volume52
Issue numberSUPPL. 17 F
StatePublished - 1993
Externally publishedYes

Keywords

  • bronchial lavage
  • early detection
  • immunocytochemistry
  • lung cancer

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Medicine(all)

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    Scott, F., Cuttitta, F., Treston, A. M., Avis, I., Gupta, P., Ruckdeschel, J., Kelly, K., Piantadosi, S., Tockman, M., & Mulshine, J. (1993). Prospective trial evaluating immunocytochemical-based sputum techniques for early lung cancer detection: Assays for promotion factors in the bronchial lavage. Journal of Cellular Biochemistry, 52(SUPPL. 17 F), 175-183.