Bcl-2 Protein Expression is Associated with a Prognostically Favourable Phenotype in Breast Cancer Irrespective of P53 Immunostaining

Aim: A role for altered programmed cell death in cancer stems from the description of alterations on tumour-associated genes involved in the regulation of apoptosis such as p53 and bcl-2. The balance between the latter may have significant implications for the pathobiology of breast cancer. This study was therefore undertaken to evaluate the expression of these two gene products with opposite functions.

Methods And Results: A total of 142 paraffin-embedded tumour blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 immunohistochemistry. The results were semiquantitated. The bcl-2 protein was found within the infiltrating neoplastic cells of 97 (68%) specimens but it was also detectable in tumours' in situ compartments and in benign mammary tissue. We identified a strong correlation between bcl-2 immunoreactivity and oestrogen receptor positivity (P = 0.03), while bcl-2 expression also correlated significantly with small tumour size (P = 0.006) and low nuclear grade (P = 0.01), but it did not correlate with the expression of p53. bcl-2 presence tended to diminish with disease progression (P = 0.06). Quantitatively increased bcl-2 immunostaining was significantly associated with older patients (P = 0.02) as well as with presence of progesterone receptors (P = 0.01). Thirty-seven tumours (26%) were judged positive for p53 protein expression. The p53 positivity status was independent of all classical histopathological variables; however, high p53 expression was negatively linked to oestrogen receptors (P = 0.005).

Conclusion: In breast cancer, bcl-2 protein is associated with a prognostically favourable phenotype and appears to be related to hormonal regulation, rather than to disabled p53 gene function.