Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables.
BACKGROUND
Bel-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. Bcl-2 is physiologically expressed in ductal epithelia of the normal breast. The biological significance of Bcl-2 (over)expression for the development and progression of breast cancer has still to be evaluated.


METHODS
A series of 133 primary breast cancers was investigated for expression of the Bcl-2 protein by immunohistochemistry of paraffin-embedded tissue sections. Results were correlated with other variables of established or presumed predictive value.


RESULTS
A significant positive correlation was observed between Bcl-2 expression and positivity for estrogen and progesterone receptors (p < 0.001). High proliferative activity as assessed by Ki-67 staining correlated inversely with Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p = 0.04), whereas a strong positive correlation was found with expression of c-erbB-3 (p = 0.01). There was a significant inverse correlation between histological grading and immunoreactivity for Bcl-2 (p < 0.001). N0 tumors tended to be Bcl-2 positive, but differences were not statistically significant.


CONCLUSIONS
Bcl-2 was detected predominantly in differentiated tumors. Expression was associated with other favorable histopathological features and predictors of positive clinical outcome. Loss of Bcl-2 expression seems to be linked to loss of hormonal regulatability, increased dedifferentiation and deregulated proliferation.
Binder
C
C
Department of Haematology/Oncology, Georg-August-University, Göttingen, Germany.
Marx
D
D
Overhoff
R
R
Binder
L
L
Schauer
A
A
Hiddemann
W
W
D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone