Biological indicators of aggressiveness in T1 ductal invasive breast cancer.
BACKGROUND
Apoptosis plays an important role in the maintenance of tissue homeostasis. When defective, this process could contribute to the pathogenesis and the progression of tumors. On this basis, we investigated the combined effect of Bcl-2 and Bax expression, known regulators of apoptotic processes, in the activation of apoptosis in breast cancer. Their relationship with DNA content and proliferative activity was also studied in order to more accurately define breast cancer patients' prognosis and treatment.


METHODS
In this study we investigated 76 T1 ductal invasive breast cancers and 76 normal epithelium samples for Bcl-2 and Bax expression by immunohistochemistry, for apoptosis by tunel assay and for DNA content and proliferative activity by flow cytometry.


RESULTS
High levels of Bcl-2 were associated with prevention of apoptosis. Conversely high Bax expression was found to be related to apoptosis. DNA ploidy was strictly related to the proliferative activity. In addition most of the tumors showing high Bcl-2 expression were aneuploid.


CONCLUSIONS
This report suggests that Bax over-expression could accelerate apoptotic cell death by counteracting the ability of Bcl-2 to inhibit apoptosis. These data also suggest that the ratio Bcl-2/Bax and their relationship with the activation of apoptosis could be used as predictive indicators of breast cancer patients' prognosis and response to conventional therapy.
Bucci
B
B
Centro Ricerca San Pietro Fatebenefratelli Hospital, Rome, Italy. bbucci_2000@yahoo.it
Carico
E
E
Rinaldi
A
A
Froio
F
F
Puce
Y M
YM
D'Agnano
I
I
Vecchione
A
A
Brunetti
E
E
D000368:Aged; D000782:Aneuploidy; D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D003593:Cytoplasm; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004171:Diploidy; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012189:Retrospective Studies; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein