Horst David, Reu Simone, Kriegl Lydia, Engel Jutta, Kirchner Thomas, Jung Andreas
Pathologisches Institut der Ludwig-Maximilians-Universität, Munich, Germany.
Cancer. 2009 May 15;115(10):2063-70. doi: 10.1002/cncr.24254.
Most colon cancers harbor mutations of APC or beta-catenin, both of which may lead to nuclear beta-catenin accumulation in the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear beta-catenin accumulation is heterogeneous throughout the tumor and often confined to the tumor margin. Herein, 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.
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.
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.
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.
大多数结肠癌存在APC或β-连环蛋白突变,这两者均可导致肿瘤细胞中β-连环蛋白在细胞核内蓄积,并使其靶基因的表达持续激活。然而,在许多结肠癌中,细胞核β-连环蛋白的蓄积在整个肿瘤中是异质性的,且常局限于肿瘤边缘。在此,作者研究了细胞核β-连环蛋白的瘤内分布是否可作为IIA期结肠癌患者生存和肿瘤进展的预后标志物。
本研究共纳入142例接受了原发肿瘤切除的中度分化IIA期结肠癌患者。通过对肿瘤的免疫组织化学染色全组织切片评估细胞核β-连环蛋白表达模式,并使用单变量和多变量统计分析将其与癌症特异性生存和无病生存相关联。
确定了四种不同的细胞核β-连环蛋白表达模式,并区分了两大类,即细胞核β-连环蛋白在瘤内有或无调节的肿瘤。此外,结果表明,这种模式,尤其是细胞核β-连环蛋白表达的调节或无调节,是患者生存和肿瘤进展的有力预测标志物。
目前的结果表明,细胞核β-连环蛋白表达的分布可作为IIA期结肠癌患者良好的预后标志物。因此,评估细胞核β-连环蛋白可能有助于识别生存期短于平均水平的患者以及疾病进展风险较高的患者,这些患者未来可能需要考虑辅助治疗方式和强化临床随访。