The Intratumoral Distribution of Nuclear β-Catenin Is a Prognostic Marker in Colon Cancer
The Intratumoral Distribution of Nuclear β-Catenin Is a Prognostic Marker in Colon Cancer
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DOI：
10.1002/cncr.24254
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发表时间：
2009-05-15
期刊：
影响因子：
6.2
通讯作者：
Jung, Andreas
中科院分区：
文献类型：
--
作者：
Horst, David;Reu, Simone;Jung, Andreas
背景：大多数结肠癌都存在APC或β -连环蛋白突变，这两种突变都可能导致核β -连环蛋白在肿瘤细胞中积累，并组成性地激活其靶基因的表达。然而，在许多结肠癌中，核β -连环蛋白的积累在整个肿瘤中是不均匀的，通常局限于肿瘤边缘。然而，作者研究了核β -连环蛋白在肿瘤内的分布是否可以作为IIA期结肠癌患者生存和肿瘤进展的预后标志物。方法：本研究共纳入142例初步切除的中分化期IIA期结肠癌患者。核β -连环蛋白的表达模式在免疫组织化学染色的整个肿瘤组织切片上进行评估，并使用单变量和多变量统计分析与癌症特异性生存和无病生存相关。结果：鉴定出4种不同的核β -catenin表达模式，并区分出核β -catenin在瘤内调节或不调节的2大类肿瘤。此外，结果表明，模式，特别是核β -连环蛋白表达的调节或不调节，是患者生存和肿瘤进展的一个强有力的预测指标。结论：目前的研究结果表明，核β -连环蛋白的表达分布可作为IIA期结肠癌患者预后的良好指标。因此，核β -连环蛋白的评估可能有助于识别那些生存期短于平均水平的患者和疾病进展风险较大的患者，这些患者可能会被考虑采用辅助治疗方式，并在未来加强临床护理。癌症2009;115:2063 - 70。(c) 2009美国癌症协会。
BACKGROUND: Most colon cancers have harbored mutations of APC or beta-catenin, both of which may lead to nuclear beta-catenin accumulation in the the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear beta-catenin accumalation were heterogeneous throughout the tumor and often confined to the tumor margin. However, the authors investigated whether the intratumoral distribution of nuclear beta-catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients. METHODS: In total, 142 patients with primarily resected, moderately differentiated stage IIA colon cancer were included in this study. The patterning of nuclear beta-catenin expression was evaluated on immunohistochemically stained whole tissue sections of the tumors and was correlated with cancer-specific survival and disease-free survival using univariate and multivariate statistical analyses. RESULTS: Four distinct patterns of nuclear beta-catenin expression were identified, and 2 main categories comprising tumors with or without intratumoral regulation of nuclear beta-catenin were distinguished. Moreover, the results demonstrated that the patterning, and especially the regulation or absence of regulation of nuclear beta-catenin expression, was a strong predictive marker of patient survival and tumor progression. CONCLUSIONS: The current results indicated that the distribution of nuclear beta-catenin expression can be used as a good prognostic marker in patients with stage IIA colon cancer. Thus, the evaluation of nuclear beta-catenin may help to identify patients who will have a shorter than average survival and patients with a greater risk of disease progression who may be considered for adjuvant therapeutic modalities and intensified clinical aftercare in the future. Cancer 2009;115:2063-70. (c) 2009 American Cancer Society.