The validation of PCNA immunohistochemical staining as a measure of cell proliferation

Proliferating cell nuclear antigen (PCNA) was evaluated as a measure of cell proliferation through comparative studies in fixed, paraffin embedded tissue labeled with either tritiated thymidine ($\sp3$H-Tdr) or 5-bromo-2$\sp\prime$-deoxyuridine (BRDU). Chemically treated and untreated samples from rat and mouse liver and mouse skin were quantitatively analyzed by both PCNA immunohistochemical staining and DNA precursor labeling. PCNA staining described similar areas of proliferative activity as $\sp3$H-Tdr and BRDU labeling. In the liver, all methods behaved similarly and detected a significant treatment effect in hepatocytes and bile duct cells. PCNA analysis found no differences between treated and untreated skin epithelial cells due to the large number of positive cells. PCNA staining is an acceptable method of measuring cell proliferation in organs with a slow turnover rate, such as liver, but it may lose sensitivity and be unsuitable in organs where there is continuous cell turnover, including skin.