β-catenin and p53 analyses of a breast carcinoma tissue microarray
β-catenin and p53 analyses of a breast carcinoma tissue microarray
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DOI：
10.1002/cncr.20232
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发表时间：
2004-05-15
期刊：
影响因子：
6.2
通讯作者：
Rimm, DL
中科院分区：
文献类型：
--
作者：
Chung, GG;Zerkowski, MP;Rimm, DL
背景β-连环蛋白信号通路的异常激活与包括乳腺癌在内的几种恶性肿瘤有关。最近，研究表明p53以复杂的方式下调P-连环蛋白。作者检测了P-catenin（其信号通路的关键成员）和p53在一个大型乳腺肿瘤队列中的表达。作者对346例淋巴结阴性乳腺癌的组织微阵列进行了β-连环蛋白、上游调节因子（HER-2/neu、Met和表皮生长因子受体[EGFR]）、下游靶基因（细胞周期蛋白D1和基质金属蛋白酶-7 [MMP 7]）和p53表达的免疫组织化学分析。这些结果彼此相关，并与标准临床病理参数相关。在膜和/或细胞质中观察到β-连环蛋白表达，而没有任何显著的核表达。HER-2/neu和EGFR分别在21%和6%的肿瘤中在膜上观察到，并且Met在28%的病例中在膜/细胞质分布中染色。细胞周期蛋白D1表达于细胞核，MMP 7表达于细胞质，分别为26%和75%的肿瘤。31%的肿瘤细胞核表达p53。当分别分析每个标记物时，只有p53和Met表现出与存活率显著相关。然而，肿瘤同时表达高水平β-连环蛋白和p53的患者总体生存率明显较差（P = 0.0026）。在多变量分析中，只有Turner大小、Met、β-catenin和p53的共表达保持统计学意义。目前的研究结果支持异常β-连环蛋白调节和p53状态在淋巴结阴性乳腺癌的发病机制和自然史中的潜在协同作用。此外，结果表明，多个标志物，特别是β-连环蛋白和p53的组合分析，可以提高预后能力相比，单独的标志物。(C)2004年美国癌症协会。
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.