Although many histologic criteria have been utilized to help distingui
sh benign from malignant adrenocortical tumors, it still may be diffic
ult to assess the biologic potential of a given tumor. We evaluated 19
adenomas and 15 primary carcinomas with the avidin-biotin complex per
oxidase method utilizing formalin-fixed, paraffin-embedded tissues wit
h monoclonal antibodies for proliferating cell nuclear antigen (PC10)
and Ki-67 (MIB 1) to determine if staining for these antigens could be
used to help differentiate benign from malignant adrenocortical neopl
asms. We also evaluated whether these markers could be used as prognos
tic indicators. Labeling indices for both PCNA and Ki-67 were determin
ed by enumerating 1000 tumor cells, and expressed as a percentage of c
ells with nuclear staining. A PCNA and a Ki-67 score was obtained by t
he product of the staining intensity (0-3+) and the extent of nuclear
staining, expressed as an estimate of the percentage of cells staining
. Both PCNA and Ki-67 score and labeling index were correlated with mi
totic counts, histologic diagnosis, and clinical outcome. Follow-up pe
riod for patients ranged from 4 months to 12 years with a mean of 25 m
onths. Mitotic counts correlated with histologic diagnosis and clinica
l outcome. Both Ki-67 score and labeling index were significantly high
er in malignant than in benign tumors, and correlated with mitotic cou
nts and clinical outcome. There was a strong correlation between Ki67
score and labeling index, indicating that Ki-67 score may be a more ra
pid and equally accurate method of estimating proliferative index of a
tumor. PCNA score and labeling index did not correlate with histologi
c diagnosis or clinical outcome. These results indicate that monoclona
l antibody MIB 1 (Ki-67) can aid in the distinction between adrenocort
ical adenomas and carcinomas in routinely processed formalin-fixed, pa
raffin-embedded tissue sections.