Multivariate analysis of bcl-2, apoptosis, P53 and HER-2/neu in breast cancer: a short-term follow-up.
BACKGROUND
Several molecular genetic alterations in breast cancer, including aneuploidy, altered apoptosis, aberrant expression of p53, HER-2/neu and Bcl-2, have been associated with poor prognosis in breast cancer patients. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathological prognostic factors, multivariate analysis was performed.


METHODS
Ninety-four fresh tissue samples of primary breast carcinoma were studied with flow cytometry for DNA ploidy. On the same specimens, steroid hormone receptors (ER and PR) were measured in the cytosol fraction using Abbott ELISA assays. HER-2/neu was determined in the membrane fraction and mutant p53 protein in the nuclear fraction, both, by Oncogene Science ELIZA procedures. Bcl-2 and apoptosis (cell death) were measured in cell lysates by Oncogene Science & Boehringer Mannheim ELISA assays. In addition, information regarding surgical-pathological features of the tumor was obtained. Multivariate analysis using an unconditional logistic regression model was done to identify variables predictive of poor prognosis.


RESULTS
Using univariate analysis, histological grade, tumor stage, lymph node status, HER-2/neu and mutant p53 were predictive of poor short-term prognosis. By multivariate analysis, tumor stage, lymph node status and HER-2/neu were independent factors. Grade subgroup analysis versus time of relapse, illustrated a predictive value of Bcl-2 in only low-grade tumors while apoptosis was significant in high-grade type.


CONCLUSIONS
Among a panel of molecular-genetic factors investigated, HER-2/neu was the most strongly predictive of poor short-term prognosis in breast cancer. Patients with HER-2/neu-positive tumors can benefit from Herceptin therapy.
el-Ahmady
O
O
Biochemistry Department, Ain Shams Faculty of Pharmacy, Cairo, Egypt.
el-Salahy
E
E
Mahmoud
M
M
Wahab
M Abdel
MA
Eissa
S
S
Khalifa
A
A
D000328:Adult; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53