Cell Kinetic Evaluation of Bromodeoxyuridine and Proliferating Cell Nuclear Antigen Expressed Cells in Experimental Bladder Tumorigenesis Using Color-Image Analysis

Lee, Hyun Moo; Kim, Wun Jae; Choi, Hwang

Abstract

A study was carried out to define the role of color-image analysis in evaluation of immunohistochemically labeled cells using anti-BrdU monoclonal antibody and anti-PCNA/cyclin monoclonal antibody, and to clarify the characteristic of nodular or papillary hyperplasia lesion using color-image analysis. Sequential cellular changes(normal, simple hyperplasia, nodular or papillary hyperplasia, and transitional cell carcinoma-Ta, T1) were observed in Fisher 344 rat urinary bladder depending on the duration of BBN administration. The mean BrdU labeling index obtained using color-image analysis and visual analysis showed statistically significant difference between normal and simple hyperplasia, and nodular or papillary hyperplasia and bladder tumor, but no difference between simple hyperplasia and nodular or papillary hyperplasia. The mean PCNA labeling index obtained by color-image analysis and visual analysis in normal, simple hyperplasia, nodular or papillary hyperplasia and bladder tumor. showed statistically significant difference in each histological group. But coefficient of variation of mean BrdU labeling index obtained by color-image analysis was higher than that by visual analysis only in normal bladder mucosa, and was lower in simple hyperplasia, nodular. or papillary hyperplasia, and bladder tumor. Coefficients of variation of mean PCNA labeling index obtained by color-image analysis were lower than those using visual analysis in all lesions. Higher BrdU and PCNA labeling indices indicated greater biological malignant potential,and mean labeling index in each histological group obtained by both color-image and visual analyses progressively increased with tumorigenesis. The coefficients of variation with color-image analysis were lower than those with visual analysis in general, therefore. the evaluation of labeling indices obtained using color-image analysis was more reliable than that obtained using visual analysis. Nodular or papillary hyperplasia showed rather a premalignant lesion in dynamic process than the previous concept of two separated entities, reversible or irreversible lesion, when evaluated more reliably by color-image analysis. The data suggest that cell kinetic evaluation using color-image analysis provide more reliable information to evaluate immunohistochemical staining in terms of quantitation and reproducibility and play an important role in predicting proliferative activity and malignant potential for bladder tumor.