Background: In breast cancel; nuclear volume estimates can be expected to b
e better prognosticators than nuclear profile areas because biological vari
ation is wider in volume estimates than in area measurements. Materials and
Methods: 191 invasive breast cancel samples were available for nuclear vol
ume measurements. To estimate the volume weighted mean nuclear volume, poin
t-sampled linear intercepts were used on micrographs. The nuclear profile a
rea was measured from 148 cases matching volume measurements and run by the
Prodit morphometry program. Measurements were compared as prognosticators
after a follow-up of 5 years. A computerized method on a randomly selected
large number of nuclei was also applied in 17 cases. Bcl-2 immunostaining w
as compared with nuclear measurements. Results: The correlation of volume a
nd area measurements was statistically significant, but the correlation coe
fficients were low. The nuclear area showed a significant difference in sur
vival at the 75 percentile cut-point but the volume-weighted mean nuclear v
olume did not allow distinction of different prognostic groups. Computerize
d volume measurements based on a large number of nuclei and measurements ba
sed on the simpler method did not show statistically significant correlatio
n. Bcl-2 staining did not show any correlation with volume or area measurem
ents. Conclusions: Although the prognostic value of nuclear area was shown
in our study, the volume-weighted mean nuclear volume did not show prognost
ic significance. Improvement of the methodology which could decrease method
variation and increase reproducibility of measurements is urgent for verif
ication of the prognostic value of nuclear volume measurements. Bcl-2 immun
ostaining and nuclear area measurements were independent prognostic variabl
es.