Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3 has a synergistic negative prognostic effect on breast carcinoma survival

被引:88
作者
Wiseman, SM
Makretsov, N
Nielsen, TO
Gilks, B
Yorida, E
Cheang, M
Turbin, D
Gelmon, K
Huntsman, DG
机构
[1] St Pauls Hosp, Dept Surg, Vancouver, BC V6Z 1Y6, Canada
[2] Vancouver Gen Hosp, Prostate Res Ctr, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada
[3] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada
[4] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada
关键词
HER-1; HER-2; HER-3; HER-4; tissue microarray; breast carcinoma; prognosis;
D O I
10.1002/cncr.20970
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. The clinical significance of coexpression of type 1 growth factor receptor (T1GFR) family members remains largely unknown. The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER-1, HER-2, HER-3, and HER-4 by breast carcinoma. METHODS. Tissue microarrays were constructed using clinically annotated formalin-fixed, paraffin -embedded tumor samples from 242 patients with invasive breast carcinomas with a median 15-year follow-up. The levels of T1GFR family members (HER-1-HER-4) were measured by immunohistochemistry. K-means clustering algorithm, as well as univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) survival analyses were applied to the data set. RESULTS. Using univariate analysis, expression of HER-1, HER-2, and HER-3, but not HER-4, was significantly associated with decreased patient disease-specific survival (P < 0.05). Kaplan-Meier survival analysis showed that coexpression of >= 2 of HER-1, HER-2, and HER-3 in any combination was associated with reduced patient disease-specific survival compared with single marker expression or no expression (35% vs. 65% vs. 78% 10-year survival rates, P = 0.001). Using multivariate analysis, expression of >= 2 of HER-1, HER-2, and HER-3 was independent of lymph node status and turner size. CONCLUSIONS. In a cohort of patients with breast carcinoma, the authors observed T1GFR family member coexpression (HER-1, HER-2, and HER-3) to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status. Thus, coexpression of T1GFR family members identified a subset of patients with a poor disease prognosis who may potentially benefit from therapy simultaneously targeting several T1GFR family members. (c) 2005 American Cancer Society.
引用
收藏
页码:1770 / 1777
页数:8
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