COMPARATIVE-ANALYSIS OF PROLIFERATING CELL NUCLEAR ANTIGEN, BROMODEOXYURIDINE, AND MITOTIC INDEX IN UVEAL MELANOMA

Purpose, Recent production of a monoclonal antibody, PC10, against pro liferating cell nuclear antigen (PCNA) makes it possible to evaluate c ell cycling in formalin-fixed tissues. In this study, the authors quan titatively evaluated the relationship between PCNA expression and two other measures of cell cycling, bromodeoxyuridine labeling index (BrdU LI) and mitotic index (MI), in archival uveal melanomas. The authors also examined the relative prognostic importance of each measure. Meth ods, Serial sections from 35 formalin-fixed, paraffin-embedded uveal m elanomas were immunostained with PC10 and BrdU antibody using a standa rd avidin-biotin-peroxidase method. A quantitative scoring system was used to evaluate the fraction of cells that were positive for PCNA, Br dU, and mitotic figures in the regions of high cycling. The LIs of the different markers were compared, and their prognostic importance was evaluated. Results, The median PCNA LI was 3.05% compared to the media n BrdU LI of 0.94% and the median MI of 0.034%. The PCNA LI was more v ariable in replicate sections than either the MI or the BrdU LI. The c orrelation between PCNA LI and BrdU LI was 0.58, between PCNA LI and M I it was 0.46, and between BrdU LI and MI it was 0.81. The relative ri sk of tumor-related mortality per doubling of BrdU LI was 2.35, and of MI it was 2.34. Although these were significant, PCNA LI of 1.08 was not. Conclusions, Proliferating cell nuclear antigen immunostaining di d not demonstrate a strong relationship with either BrdU LI or MI. Unl ike MI and BrdU LI, PCNA LI was not correlated with tumor-related mort ality. Caution is warranted in the interpretation of PCNA immunostaini ng in uveal melanomas.