Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases.
To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.
Rudolph
P
P
Department of Pathology and Lymph Node Registry at the German Association of Pathologists, University of Kiel. prudolph@path.uni-kiel.de
MacGrogan
G
G
Bonichon
F
F
Frahm
S O
SO
de Mascarel
I
I
Trojani
M
M
Durand
M
M
Avril
A
A
Coindre
J M
JM
Parwaresch
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000276:immunology* / Q000401:mortality; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II