c-erbB2 and topoisomerase IIalpha protein expression independently predict poor survival in primary human breast cancer: a retrospective study.
BACKGROUND
c-erbB2 (also known as HER-2/neu) and topoisomerase IIalpha are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIalpha protein influences the long-term outcome of patients with primary breast cancer.


METHODS
In this study c-erbB2 and topoisomerase IIalpha protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed.


RESULTS
Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIalpha protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIalpha overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIalpha was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIalpha showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIalpha or c-erbB2 overexpression.


CONCLUSIONS
The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIalpha in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer.
Fritz
Peter
P
Department of Diagnostic Medicine, Pathology, Robert Bosch Hospital, Stuttgart, Germany. peter.fritz@rbk.de
Cabrera
Cristina M
CM
Dippon
Jürgen
J
Gerteis
Andreas
A
Simon
Wolfgang
W
Aulitzky
Walter E
WE
van der Kuip
Heiko
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases