Stereologic estimation of nucleolar volume in ocular melanoma: a comparative study of size estimators with prognostic...

The aim of this study was to investigate the relationships between one-, two-, and three-dimensional histomorphometric estimators of nucleolar size in ordinary histologic sections of uveal melanomas from 144 patients. In addition, the prognostic value of the various size parameters was studied. The following estimates were obtained: the mean diameter of the 10 largest nucleoli, the mean nucleolar profile area and associated standard deviation of the nucleolar profile area, the volume-weighted mean nucleolar volume (nucleolar vv), and the macroscopic, largest tumor dimension. All histomorphometric parameters were highly intercorrelated (r > .75). The correlation between the largest tumor dimension and the nucleolar vv was rather poor (r = .35). The efficiency of the sampling scheme for estimation of the nucleolar vv was very high; more than 95% of the totally observed variation was contributed by biologic differences between tumors. Single-term Cox analyses demonstrated a highly significant prognostic value of all five investigated, quantitative variables. Evaluation in a multivariate Cox model showed, however, that only the nucleolar vv and the largest tumor dimension were independent prognostic covariates at the chosen level of significance (5%). Unbiased, shape-independent estimates of the nucleolar vv offered superior prediction of clinical outcome, as compared with lower-dimensional, shape-dependent histomorphometric estimators of nucleolar size.