β-catenin and p53 analyses of a breast carcinoma tissue microarray

被引:73
作者
Chung, GG
Zerkowski, MP
Ocal, IT
Dolled-Filhart, M
Kang, JY
Psyrri, A
Camp, RL
Rimm, DL
机构
[1] Yale Univ, Ctr Canc, Sect Med Oncol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT USA
关键词
breast carcinoma; beta-catenin; p53; tissue microarray;
D O I
10.1002/cncr.20232
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. Aberrant activation of the beta-catenin signaling pathway has been implicated in several malignancies, including breast carcinoma. Recently, it was shown that p53 down-regulated P-catenin in a complex fashion. The authors examined the expression of P-catenin, key members of its signaling pathway, and p53 in a large cohort of breast tumors. METHODS. The authors conducted an immunohistochemical analysis of the expression of beta-catenin, upstream modulators (HER-2/neu, Met, and epidermal growth factor receptor [EGFR]), downstream target genes (cyclin D1 and matrix metalloproteinase-7 [MMP7]), and p53 on a tissue microarray of 346 lymph node-negative breast carcinomas. The results were correlated with one another and with standard clinicopathologic parameters. RESULTS. p-Catenin expression was observed in the membrane and/or cytoplasm without any significant nuclear expression. HER-2/neu and EGFR were observed on the membrane in 21% and 6% of tumors, respectively, and Met stained in a membrane/ cytoplasm distribution in 28% of cases. Cyclin D1 was expressed in the nucleus and MMP7 was expressed in the cytoplasm in 26% and 75% of tumors, respectively. Nuclear expression of p53 was noted in 31% of tumors. When each marker was analyzed separately, only p53 and Met demonstrated a significant correlation with survival. However, patients who had tumors that coexpressed high levels of beta-catenin and p53 had markedly worse overall survival (P = 0.0026). In multivariate analysis, only turner size, Met, and the coexpression of beta-catenin and p53 retained statistical significance. CONCLUSIONS. The current findings support a potential synergistic effect of abnormal beta-catenin regulation and p53 status in the pathogenesis and natural history of lymph node-negative breast carcinoma. Furthermore, the results show that a combined analysis of multiple markers, notably beta-catenin and p53, may enhance the prognostic capabilities compared with individual markers. (C) 2004 American Cancer Society.
引用
收藏
页码:2084 / 2092
页数:9
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