Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE-3 in breast-cancer prognosis.
Taking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE-3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE-3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin-embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to Kaplan-Meier univariate and Cox proportional-hazards multi-variate analysis. Additionally, traditional prognostic variables for breast-cancer prognosis (grade of differentiation, age, tumor size, axillary-lymph-node involvement and estrogen receptors) were subjected to identical analyses. In uni-variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi-variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary-node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni-variate and multi-variate level. A multi-variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary-node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub-populations of patients with infiltrating breast carcinoma with defined risk functions.
Ceriani
R L
RL
John Muir Cancer and Aging Research Institute, Walnut Creek, CA 94596.
Chan
C M
CM
Baratta
F S
FS
Ozzello
L
L
DeRosa
C M
CM
Habif
D V
DV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C057387:mucinous carcinoma-associated antigen