Nuclear expression of thioredoxin-1 in the invasion front is associated with outcome in patients with gallbladder carcinoma

Nuclear expression of thioredoxin-1 in the invasion front is associated with outcome in patients with gallbladder carcinoma
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DOI:
10.1111/j.1477-2574.2012.00482.x
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发表时间:
2012-09-01
期刊:
HPB
影响因子:
2.9
通讯作者:
Chijiiwa, Kazuo
Chijiiwa, Kazuo
中科院分区:
医学3区
文献类型:
--
作者:
Nagano, Motoaki;Hatakeyama, Kinta;Chijiiwa, Kazuo

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背景:多功能氧化还原蛋白人硫氧还蛋白(TRX-1)被硫氧还蛋白还原酶(TRX-R)还原。本研究的目的是检测TRX-1和TRX-R在胆囊癌(GBC)中的表达分布,以阐明它们作为手术切除后预后因素的有效性。方法:对38例手术切除的胆囊癌组织进行TRX-1和TRX-R免疫组织化学染色,分析TRX-1/TRX-R定位与预后的关系。结果:胆囊癌组织中Trx-1蛋白水平显著高于胆囊结石组织(P=0.0174)。TRX-1在100%(38/38)的肿瘤组织中表达,76%(29/38)的肿瘤组织有核表达,45%(13/29)的肿瘤组织有核表达。TRX-R仅在癌细胞胞浆和侵袭前沿表达,28例中仅在癌细胞胞浆中表达。单因素分析显示,肿瘤侵袭深度、淋巴结转移、手术切缘、侵袭前沿TRX-1的可治性和核表达是影响预后的重要因素。在选择行根治性切除的27例患者中,侵袭前线的TRX-1核表达和TRX-R胞浆表达均是显著的预后因素。结论:TRX-1在胆囊癌侵袭前沿的核表达是一个重要的预后指标。肿瘤侵袭前沿既有TRX-1核表达,又有TRX-R胞浆表达的患者,即使在根治性切除后也应仔细观察。
Background: Multifunctional redox protein human thioredoxin (TRX-1) is reduced by thioredoxin reductase (TRX-R). The aim of the present study was to examine the distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to clarify their usefulness as prognostic factors after surgical resection. Methods: Immunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from 38 patients who underwent surgical resection, and TRX-1/TRX-R localization in relation to outcome was examined. Results: TRX-1 protein levels were significantly higher in GBC samples than in cholecystolithiasis samples (P= 0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in the nucleus in 76% (29/38), with nuclear expression in the invasion front observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of cancer cells and in the invasion front in 28 samples. In all of the samples, the depth of tumour invasion, lymph node metastasis, surgical margin, curability and nuclear expression of TRX-1 in the invasion front were significant prognostic factors by univariate analysis. In 27 selected patients who underwent curative resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the invasion front was a significantly prognostic factor. Conclusion: TRX-1 nuclear expression in the GBC invasion front is a significant prognostic marker. Patients with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour invasion front should be observed carefully even if after curative resection.