In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.
Bronchial Neoplasms/*genetics/pathology ; Carcinoma, Squamous Cell/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; DNA ; Humans ; Metaplasia ; Nucleic Acid Hybridization ; *Oncogenes