Morphometric characteristics of cell proliferation and p53 expression in development of experimentally induced respiratory tumors

OBJECTIVE: To study, under controlled conditions, the applicability of auto mated image analysis of immunohistochemical markers as an indicator of deve lopment and progression in tobacco component-induced tumors in the respirat ory tract. TUDY DESIGN: Amount, location, size, shape and intensity of staining of pro liferating cell and p53 antigen in chemically induced precursors and squamo us cell carcinoma of the hamster lung were determined by computer-assisted morphometry. RESULTS: The total expression of proliferating cell nuclear antigen (PCNA) and p53 expression increased consistently during the formation of papilloma s and squamous cell carcinomas of the larynx, trachea, bronchi and lungs. I ndividual preneoplastic cells in epithelial dysplasia expressed PCNA staini ng, increasing with increasing cell size and optical density, indicating an tibody-staining intensity, in relation to the increased degree of cellular atypia. In malignant tumors, cell size decreased with decreasing differenti ation, while antibody staining intensity remained unchanged. The increased alterations in cell shape and percent PCNA-positive cells observed in dyspl astic epithelium and squamous cell carcinomas were statistically significan t using Spearman's correlation coefficient. Squamous cell carcinomas consis ted of two tumor cell populations with different cell shapes, and PCNA and p53 staining intensity. Altering measurement conditions - antibody threshol d levels, size of measured area and repeating measurements - showed compute r-assisted image analysis to give sensitive, reliable and consistent result s. CONCLUSION: Computer-assisted analysis of immunohistochemical staining show ed high sensitivity and reproducibility; however, the results depended upon the method of study.