Comparative analysis of proliferating cell nuclear antigen, bromodeoxyuridine, and mitotic index in uveal melanoma.

PURPOSE

Recent production of a monoclonal antibody, PC10, against proliferating cell nuclear antigen (PCNA) makes it possible to evaluate cell cycling in formalin-fixed tissues. In this study, the authors quantitatively 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.

METHODS

Serial sections from 35 formalin-fixed, paraffin-embedded uveal melanomas were immunostained with PC10 and BrdU antibody using a standard avidin-biotin-peroxidase method. A quantitative scoring system was used to evaluate the fraction of cells that were positive for PCNA, BrdU, 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 median BrdU LI of 0.94% and the median MI of 0.034%. The PCNA LI was more variable in replicate sections than either the MI or the BrdU LI. The correlation between PCNA LI and BrdU LI was 0.58, between PCNA LI and MI it was 0.46, and between BrdU LI and MI it was 0.81. The relative risk 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 did not demonstrate a strong relationship with either BrdU LI or MI. Unlike MI and BrdU LI, PCNA LI was not correlated with tumor-related mortality. Caution is warranted in the interpretation of PCNA immunostaining in uveal melanomas.