Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer.
BACKGROUND
The use of adjuvant chemotherapy in early breast carcinoma is controversial, with most advocating its use in high-risk patients as defined by specific clinicopathologic parameters. Both bcl-2 and p53, which play a role in determining tumor growth by their effects on apoptosis and cell proliferation respectively, may serve to delineate this subset more accurately. The purpose of this study was to determine the prognostic value of bcl-2, Bax, and mutant p53 in stage I breast cancer.


METHODS
A total of 75 patients with stage Ic breast carcinoma diagnosed from 1989 to 1992 were identified retrospectively and clinicopathologic parameters such as age, tumor size, estrogen receptor (ER) and progesterone receptor (PR) status, disease-free survival and overall survival obtained. Paraffin-embedded formalin-fixed tissues were immunostained with bcl-2, Bax and p53 monoclonal antibodies using a standard avidin biotin peroxidase reaction. Stained slides were evaluated by two independent pathologists for staining intensity and percentage of cells staining positively. Cox regression was used for multivariate survival analysis using the clinicopathologic parameters and molecular markers. Chi-square tests were used for frequency tables.


RESULTS
Mean patient age was 58 years (range 29 to 79 years) with a median followup of 80 months from time of diagnosis. The most common histopathology was infiltrating ductal carcinoma. Neither bcl-2 nor Bax expression was associated statistically with disease-free or overall survival. Expression of mutant p53 was associated with a significant decrease in both 5-year disease-free survival (70% versus 98%, p </= 0.01 in multivariate analysis) and 5-year overall survival (74% versus 100%, p = 0.03). Expression of bcl-2 was associated with hormone receptor expression and tumor diploid status. Of tumors expressing bcl-2, 36 of 49 (73%) were ER+ (p = 0.017, versus tumors not expressing bcl-2, 6 of 15 [40%]), 22 of 49 (45%) PR+ (p = 0.027 versus tumors not expressing bcl-2, 2 of 15 [13%]) and 28 of 44 (64%) diploid (p = 0.004 versus tumors not expressing bcl-2, 1 of 9 [11%]).


CONCLUSIONS
These results indicate that bcl-2 expression is significantly associated with hormonal receptor status and that p53 is a significant prognostic marker for survival in early breast cancer.
Linjawi
Ayman
A
Division of General Surgery, Division of Clinical Epidemiology, McGill University, Montreal, Quebec, Canada.
Kontogiannea
Maria
M
Halwani
Fawaz
F
Edwardes
Michael
M
Meterissian
Sarkis
S
D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012044:Regression Analysis; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein