The purpose of this study was to investigate apoptosis, proliferation, and
the expression of apoptosis-influencing proteins bcl-2 and bar and estrogen
and progesterone receptors during breast carcinoma progression. The materi
al consisted of 53 paired breast carcinoma samples representing primary and
recurrent tumors and 24 control samples. The recurrent sample was located
either in the breast scar tissue or at a distant metastatic site. Apoptosis
was detected both morphologically and by 3' end labeling of fragmented DNA
. Cell proliferation was evaluated immunohistochemically by the MIB index.
The expressions of bcl-2, bar, and estrogen and progesterone receptors were
studied immunohistochemically, There was a significant increase in the ext
ent of apoptosis and proliferation in recurrent tumors compared to the prim
ary lesions (P = 0.015 and P = 0.038, respectively). In primary tumors with
an apoptotic index of >050%, the survival of the patients was significantl
y shorter (P = 0.015), In cases with a significant increase in apoptosis or
proliferation in the recurrent tumor, the survival of the patients was sig
nificantly shorter (P = 0.009 and P = 0.003, respectively). Of the variable
s analyzed, bcl-2 expression and a positive estrogen receptor status were s
ignificantly associated with a low extent of apoptosis (P = 0.010 and P = 0
.042, respectively), Their changes were parallel to the changes in apoptosi
s during tumor progression, although the associations did not reach statist
ical significance, The results show that increased apoptosis is associated
with a worse prognosis in breast carcinoma. A significant increase in apopt
osis in recurrent breast carcinoma lesions predicts a worse clinical outcom
e.