Journal of Clinical Oncology, Vol 10, 686-695, Copyright © 1992 by American Society of Clinical Oncology
Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features
G Gasparini, WJ Gullick, P Bevilacqua, JR Sainsbury, S Meli, P Boracchi, A Testolin, G La Malfa and F Pozza
St Bortolo Regional Hospital, Vicenza-Veneto, Italy.
PURPOSE: A study was undertaken to define the prognostic value of the
expression of the c-erbB-2 oncoprotein in a series of breast cancer
patients when compared by multivariate analysis with expression of the
epidermal growth factor receptor (EGFR), DNA ploidy, and conventional
clinicopathologic features. PATIENTS AND METHODS: Prognostic indicators
were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was
recognized by the polyclonal antibody 21N using an immunocytochemical
method. Expression of the EGFR was stated immunocytochemically using the
monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded
sections using a standard flow- cytometric method. RESULTS: Overall, 27% of
carcinomas had membrane 21N- staining and were classified as
c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly
associated with EGFR expression and the conventional pathologic features,
and it was weakly associated with DNA ploidy and nodal status. Univariate
analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and
EGFR provided significant prognostic information concerning 4-year
relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of
2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS)
at 4 years, only nodal status and DNA ploidy had prognostic significance,
with the ORs of not dying of 2.68 and 2.80, respectively. Applying
multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and
DNA ploidy (full model) failed to retain prognostic value (P = .202),
whereas nodal status was the most significant indicator of relapse (P =
.027) followed by DNA ploidy (P = .056) and EGFR (P = .093). CONCLUSIONS:
This study suggests that overexpression of the c-erbB-2 oncoprotein appears
to be an important indicator of relapse in stage I- II breast cancer when
singly evaluated. Multivariate analysis shows that the determination both
of nodal status and DNA ploidy improves our ability to identify subsets of
patients with different prognoses, and allows for a better selection of
patients for systemic adjuvant treatments.
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