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胃癌中KLF4的表达及凋亡相关标志物

KLF4 expression and apoptosis-related markers in gastric cancer.

作者信息

Krstic M, Stojnev S, Jovanovic L, Marjanovic G

机构信息

Institute of Pathology, Faculty of Medicine, University of Nis, Nis, Serbia.

出版信息

J BUON. 2013 Jul-Sep;18(3):695-702.

Abstract

PURPOSE

To correlate the expression of Kruppel-like factor 4 (KLF4) with clinicopathological properties of gastric cancer (GC) and to evaluate any possible correlation between KLF4 expression and the expression of apoptosis-related markers p53, Fas, Bcl-2, survivin and FLICE inhibitory protein (Flip-l).

METHODS

Formalin-fixed, paraffin-embedded tissue specimens obtained from 96 patients with GC who had undergone gastric surgery were analyzed for pathological parameters, while KLF4, p53, Fas, Bcl-2, survivin and Flip-l expression was assessed by immunohistochemistry.

RESULTS

TKLF4 immunohistochemical staining was noted in 78.1% of the cases. Strong positivity was found in 15.6% and weak in 62.5% of the samples. Positive expression of p53, Fas, Bcl-2, survivin, Flip-l was found in 56.2%, 44.8%, 15.6%, 41.7% and 38.5% of the samples, respectively. KLF4 expression was significantly associated with p53 nuclear staining and Fas immunoreactivity. p53-positive tumors demonstrated more often high KLF4 staining compared to p53-negative tumors. Fas-positive tumors were associated with decreased KLF4 expression. Logistic regression analysis of apoptosis-related markers to KLF4 expression revealed that Fas positivity significantly decreased the probability of strong KLF4 expression, and inversely, Bcl-2 expression improved the prediction of KLF4 staining. When all 5 predictive variables were considered together (p53, Fas, survivin, Bcl-2, Flip-l) they significantly predicted the type of KLF4 expression in GC cells (p=0.019).

CONCLUSION

Our results suggest that the decrease or loss of KLF4 expression correlates with diffuse-type GC and immunoreactivity to Fas, and are inversely linked with p53 nuclear accumulation. The significance of KLF4 in GC requires further studies and should be more thoroughly investigated for potential use in the evaluation and better stratification of GC patients.

摘要

目的

探讨Kruppel样因子4(KLF4)的表达与胃癌(GC)临床病理特征的相关性,并评估KLF4表达与凋亡相关标志物p53、Fas、Bcl-2、生存素和FLICE抑制蛋白(Flip-l)表达之间的可能关联。

方法

对96例行胃手术的GC患者的福尔马林固定、石蜡包埋组织标本进行病理参数分析,同时采用免疫组织化学法评估KLF4、p53、Fas、Bcl-2、生存素和Flip-l的表达。

结果

78.1%的病例中观察到KLF4免疫组织化学染色。15.6%的样本呈强阳性,62.5%呈弱阳性。p53、Fas、Bcl-2、生存素、Flip-l的阳性表达分别见于56.2%、44.8%、15.6%、41.7%和38.5%的样本。KLF4表达与p53核染色和Fas免疫反应性显著相关。与p53阴性肿瘤相比,p53阳性肿瘤更常表现为KLF4高染色。Fas阳性肿瘤与KLF4表达降低相关。对凋亡相关标志物与KLF4表达进行逻辑回归分析显示,Fas阳性显著降低了KLF4强表达的概率,反之,Bcl-2表达改善了对KLF4染色的预测。当同时考虑所有5个预测变量(p53、Fas、生存素、Bcl-2、Flip-l)时,它们显著预测了GC细胞中KLF4表达的类型(p=0.019)。

结论

我们的结果表明,KLF4表达的降低或缺失与弥漫型GC及Fas免疫反应性相关,且与p53核积聚呈负相关。KLF4在GC中的意义需要进一步研究,应更深入地探讨其在GC患者评估和更好分层中的潜在应用。

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