Oncogenic β-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer
Oncogenic β-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer
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DOI：
10.1053/gast.2002.30306
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发表时间：
2002-01-01
期刊：
影响因子：
29.4
通讯作者：
Minamoto, T
中科院分区：
文献类型：
--
作者：
Ougolkov, AV;Yamashita, K;Minamoto, T
背景与目的：最近的体外研究表明，β-连环蛋白易位到肿瘤细胞核中，通过反式激活癌基因（包括 MMP-7）而发挥癌基因的作用。我们对人类结肠癌中的 β-连环蛋白和 MMP-7 表达进行了大规模分析，以确定这些分子的潜在临床重要性。方法：在 202 例术后结局已知的结肠癌患者中，我们通过免疫组织化学方法测定了肿瘤中 β-catenin 和 MMP-7 的表达，并将结果与患者的临床病理特征和生存情况相关联。结果：我们在结肠癌中发现了 2 种不同的 β-连环蛋白核积聚 (NA) 模式：89 例 (44%) 中的弥漫性 NA (NAd) 和 18 例 (9%) 中侵袭前沿的选择性 NA (NAinv)。 NAinv模式的存在与晚期Dukes分期（P = 0.0187）和肿瘤复发（P = 0.0005）以及肿瘤侵袭前沿的MMP-7表达显着相关（P = 0.0025），导致极其不利的临床结果。多变量分析确定 NAinv 表达模式和 Dukes C 分期是独立的预后因素。结论：以 NAinv 表达模式为代表的肿瘤侵袭前沿 β-连环蛋白的致癌激活可能是一个独立且可靠的指标，可判断极易发生肿瘤复发且生存率较差的结肠癌患者亚群。
Background & Aims: Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, Including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules. Methods: In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival. Results: We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors. Conclusions: Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate.