Expression level of the mitotic checkpoint protein and G2-M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach
Expression level of the mitotic checkpoint protein and G2-M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach
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DOI：
10.1007/s00428-011-1181-z
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发表时间：
2012-02-01
期刊：
影响因子：
3.5
通讯作者：
Oda, Yoshinao
中科院分区：
文献类型：
--
作者：
Fujita, Aya;Yamamoto, Hidetaka;Oda, Yoshinao
胃肠道间质瘤（GIST）的生物学行为从良性到恶性不等，不良结局的风险与原发肿瘤的位置、肿瘤大小和有丝分裂计数相关。细胞周期调控因子与GIST的发生和发展有潜在的相关性。叉头环指检查点（Checkpoint with forkhead and ring finger，CHFR）是细胞分裂早期和中期重要的检查点蛋白，对细胞有丝分裂起重要的调控作用。在这项研究中，我们评估了表达CHFR和几个细胞周期调控因子，包括细胞周期蛋白A，细胞周期蛋白B1，cdc 2，cdk 2，免疫组化染色在53例原发性胃GIST，并比较了免疫组化结果与临床病理因素或GIST的风险等级修改Miettinen等。53例中，18（34%）显示减少核CHFR表达。CHFR表达降低与较高的有丝分裂计数[> 5/50高倍视野（HPF）]（p = 0.039）和高风险等级（p = 0.0475）相关，但与其他细胞周期调节因子的表达无关。更高的细胞周期蛋白A标记指数（LI，> 1.5%），细胞周期蛋白B1 LI（> 0.25%），cdc2 LI（> 1.16%），Ki-67 LI（> 4.9%），有丝分裂计数（> 5/50 HPF）和高危分级分别与较短的无病生存期相关。（分别为p = 0.0017、p = 0.003、p = 0.0471、p = 0.002、p < 0.001和p = 0.0017）。我们的研究结果表明，修改的风险等级和G2-M调节因子，如细胞周期蛋白A，细胞周期蛋白B1和cdc 2的表达增加是有用的预测胃GIST的生物学行为。此外，CHFR表达降低可能在较高级别GIST的增殖活性增加中发挥作用。
The biological behavior of gastrointestinal stromal tumors (GISTs) ranges from benign to malignant, and the risk of an adverse outcome is correlated with the location of the primary tumor, tumor size, and mitotic counts. Cell cycle regulators are potentially associated with the tumorigenesis and progression of GISTs. Checkpoint with forkhead and ring finger (CHFR) functions as an important checkpoint protein in the early to mid-prophase to regulate mitosis. In this study, we evaluated the expression of CHFR and several cell cycle regulators, including cyclin A, cyclin B1, cdc2, and cdk2, by immunohistochemical staining in 53 cases of primary gastric GISTs, and compared the immunohistochemical results with the clinicopathological factors or the GIST risk grades as modified by Miettinen et al. Of the 53 cases, 18 (34%) showed decreased nuclear CHFR expression. Decreased CHFR expression was correlated with higher mitotic counts [> 5/50 high-power fields (HPFs)] (p = 0.039) and a high-risk grade (p = 0.0475), but not with expression of other cell cycle regulators. Higher cyclin A labeling index (LI, > 1.5%), cyclin B1 LI (> 0.25%), cdc2 LI (> 1.16%), Ki-67 LI (> 4.9%), mitotic counts (> 5/50 HPF) and high-risk grade were each associated with shorter disease-free survival (p = 0.0017, p = 0.003, p = 0.0471, p = 0.002, p < 0.001, and p = 0.0017, respectively). Our results suggest that modified risk grade and increased expression of G2-M regulators such as cyclin A, cyclin B1, and cdc2 are useful for predicting the biological behavior of gastric GISTs. In addition, decreased CHFR expression may play a role in increased proliferative activity of higher grade GISTs.