To assess the proliferative capacity of bronchial epithelial cells, we have developed a variety of methods to identify bronchial lavage products. This is an effort to complement the sputum immunocytology approach in determining who is afflicted with early lung cancer. The details of the bronchial lavage assay methodology have been recently published. A preliminary report of the experience with the first 500 patients enrolled on this trial also has been published. Manuscripts outlining new techniques of biomarker and molecular analysis of the bronchial lavage fluid are also being submitted. We have recently submitted a manuscript that outlines the pattern of expression for the most informative early lung cancer sputum marker (p31) in respiratory epithelium. P31 was expressed both in suspected premalignant and overtly cancerous bronchial epithelial cells. This antigen was also expressed in a subset of normal appearing bronchial cells. To better characterize that cellular subpopulation, we will analyze with other molecular markers because we suspect that p31 defines a potentially important preinvasive phase of lung cancer. We have recently identified the molecular identity of p31 and found it was a heterogenous nuclear, ribonuclear protein (HnRNP). These HnRNPs are an important new class of molecules that is being intensely studied because they play an important role in RNA function. The identification of p31, a proven marker of early lung cancer, as a ribonuclear protein is an unexpected but important new finding. An analysis of the utility of p31 and the other early lung cancer marker, difucosylated Lewis X in three early detection populations demonstrates that sputum immunostaining with the two markers identifies 86% of all the lung cancers occurring in those three study populations. All of those cases identified by the two antibodies are still confined to the lung epithelium. The best existing diagnostic tests for early lung cancer picks up only 15% of cancer at that stage. This new finding carries the potential of leading to significant reductions in lung cancer mortality.
