bcl-2 and apoptosis in lymph node positive breast carcinoma.
BACKGROUND
Because bcl-2 can block apoptosis in vitro, and because lower levels of apoptosis might lead to malignant cell accumulation and therefore to a more aggressive clinical course, the authors tested the hypothesis that high bcl-2 and low apoptosis would result in a worse prognosis for breast carcinoma patients.


METHODS
Primary breast tumor specimens from 979 patients with positive axillary lymph nodes were evaluated for bcl-2 protein expression by immunohistochemistry (IHC). Apoptosis was evaluated by using IHC to detect 3' DNA fragments end-labeled with biotinylated uridine. Results were analyzed with respect to patient characteristics, prognostic factors, and clinical outcome. Median follow-up was 61 months.


RESULTS
High bcl-2 expression was significantly associated with a number of favorable prognostic factors, including a lower number of positive lymph nodes, absence of p53 protein accumulation, estrogen receptor (ER) and progesterone receptor (PR) positivity, diploidy, and a lower proliferative rate. However, although bcl-2 is generally considered a negative regulator of apoptosis, in these tumors there was no significant association between bcl-2 and apoptosis. Patients with high bcl-2 expression had significantly improved disease free survival (DFS) (P < 0.0001) and overall survival (OS) (P < 0.0001). In a multivariate analysis, bcl-2 expression was independently associated with better DFS (P = 0.004). Regarding apoptosis, the presence of > or = 1% apoptotic cells was significantly associated with a greater number of positive lymph nodes, p53 protein expression, ER and PR negativity, aneuploidy, and a higher proliferation rate, although there was no significant association with a worse clinical outcome when this dichotomized cutoff was used.


CONCLUSIONS
For lymph node positive breast carcinoma patients, high bcl-2 expression is associated with a number of good prognostic factors and is independently associated with better clinical outcome. Apoptosis is associated with a number of poor prognostic factors but not with a significantly worse outcome.
Berardo
M D
MD
Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750, USA.
Elledge
R M
RM
de Moor
C
C
Clark
G M
GM
Osborne
C K
CK
Allred
D C
DC
D017209:Apoptosis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002455:Cell Division; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate
D019253:Proto-Oncogene Proteins c-bcl-2