Differential Image Analysis of Proliferating Cell Nuclear Antigen (PCNA) Expression Level during Experimental Thyroid Carcinogenesis.

Immunostaining of proliferating cell nuclear antigen (PCNA), which can be applied to routinely processed tissue sections, has extended the applications of cell kinetic studies. PCNA immunostaining intensity of cells varies among individual nuclei in tissue sections. To determine the changes in PCNA expression level during carcinogenesis, we employed an image analyzer to evaluate PCNA staining intensity in diisopropanolnitrosamine (DIPN) -induced neoplastic lesions of rat thyroid glands.In the normal thyroid gland, only small numbers of cells showed weak PCNA expression. The percentage of PCNA-positive cells increased during carcinogenesis, i. e. hyperplasia, adenoma, and then carcinoma. Analysis of PCNA staining intensity histograms revealed that the population of cells with stronger intensity increased during carcinogenesis, i. e. from adenoma to carcinoma. However, the percentage of cells with weak PCNA staining increased in hyperplasia, and did not change in intensity during further carcinogenic sequelae. These differences in PCNA expression level recognized by immunostaining intensity may reflect different cell kinetics between the process of hyperplasia and that of differentiation from adenoma to carcinoma.