PROSPECTIVE TRIAL EVALUATING IMMUNOCYTOCHEMICAL-BASED SPUTUM TECHNIQUES FOR EARLY LUNG-CANCER DETECTION - ASSAYS FOR PROMOTION FACTORS IN THE BRONCHIAL LAVAGE

To confirm the results of a previous report on the use of monoclonal a ntibodies in immunocytochemical assays of sputums for the early detect ion of lung cancer, we designed a new prospective trial in an independ ent clinical trial population. Since well-characterized Stage I resect ed non-small cell lung cancer patients have a low rate of tumor relaps e and a high (1-3%/year) chance of developing a second primary lung ca ncer, they comprise a very favorable group for conducting an early lun g cancer detection trial. The rate of new lung cancer is about 10-fold in excess of a standard ''high'' risk population of smokers. To optim ize the chance for a favorable outcome, all of the technical component s for the trial have been systematically evaluated to ensure that opti mal procedure!s are employed. For example, automated immunostaining of the sputum specimens will be performed. Bronchial lavages will be ana lyzed in a subset of the trial participants to define additional targe ts for early lung cancer detection. Two markers will be quantitated, i ncluding gastrin releasing peptide and peptidyl glycine alpha-amidatin g monooxygenase activity. These two markers assess the epithelium's ca pacity to produce growth factors which may be central to the biology o f tumor promotion. Since these assays have not been performed in this context before, we attempted to optimize the specimen handling to perm it the receipt of the material from a range of collaborating clinical sites in a condition that permits accurate quantitation of these two b iomarkers. Efforts to standardize the assay endpoint stimulated the de velopment of computer-assisted methods of immunocytochemical analysis. An algorithm for image analysis was developed as a result of systemat ic analysis of a range of potentially quantifiable assay endpoints wit h a panel of teaching cases. When a sampling of the original immunosta ined material from the first monoclonal antibody-based early lung canc er 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 proces s of early lung cancer detection research. An update of the current tr ial status will be summarized emphasizing the unique challenges presen ted in early cancer detection research. (C) 1993 Wiley-Liss, Inc.