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吲哚胺 2,3-双加氧酶表达预测根治性子宫切除术治疗浸润性宫颈癌患者生存受损。

Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy.

机构信息

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Gynecol Oncol. 2010 Jun;117(3):423-8. doi: 10.1016/j.ygyno.2010.02.028. Epub 2010 Mar 28.

Abstract

OBJECTIVE

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that induces tolerance to host immune surveillance within the tumor microenvironment. The present study aimed to investigate IDO expression and its prognostic significance in invasive cervical cancer.

METHODS

Immunohistochemical expression of IDO in tumor tissues and its association with clinicopathological factors and survival were analyzed in 112 stage IB-IIB cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy.

RESULTS

IDO was diffusely expressed in tumor cells in 29 (26%) cases and focally expressed at the invasive front in 29 (26%) cases, while the other 54 (48%) cases were IDO-negative. IDO expression was positively correlated with clinical stage, lymph node metastasis, and lymph-vascular space invasion, but not with histological type. Patients with diffuse IDO expression had significantly reduced overall survival (OS) and disease-free survival (DFS) compared to patients with no IDO expression. The 5-year OS/DFS rates for the IDO-negative, focally positive, and diffusely positive groups were 92.3%/84.9%, 89.5%/75.8%, and 65.5%/51.7%, respectively. When we analyzed patients with stage IB disease alone (n=67), the OS and DFS for the IDO-diffusely positive group were significantly lower than those for the IDO-negative group. In multivariate analysis, diffuse IDO expression was found to be an independent prognostic factor for impaired OS and DFS.

CONCLUSIONS

Diffuse expression of IDO in the tumor obtained from Stage IB-IIB cervical cancer patients who underwent radical hysterectomy was correlated with an unfavorable clinical outcome. These findings suggest that IDO may be a novel post-operative prognostic indicator for stage IB-IIB cervical cancer.

摘要

目的

吲哚胺 2,3-双加氧酶(IDO)是一种分解色氨酸的酶,可在肿瘤微环境中诱导宿主免疫监视耐受。本研究旨在探讨 IDO 在浸润性宫颈癌中的表达及其预后意义。

方法

采用免疫组织化学方法检测 112 例接受根治性子宫切除术和盆腔淋巴结清扫术的 IB-IIB 期宫颈癌患者肿瘤组织中 IDO 的表达,并分析其与临床病理因素及生存的关系。

结果

29 例(26%)肿瘤细胞弥漫表达 IDO,29 例(26%)肿瘤细胞局灶表达 IDO,而 54 例(48%)为 IDO 阴性。IDO 表达与临床分期、淋巴结转移和脉管间隙浸润呈正相关,与组织学类型无关。弥漫性 IDO 表达患者的总生存(OS)和无病生存(DFS)显著低于无 IDO 表达患者。IDO 阴性、局灶阳性和弥漫阳性组的 5 年 OS/DFS 率分别为 92.3%/84.9%、89.5%/75.8%和 65.5%/51.7%。当我们单独分析 IB 期患者(n=67)时,IDO 弥漫阳性组的 OS 和 DFS 明显低于 IDO 阴性组。多因素分析显示,弥漫性 IDO 表达是 OS 和 DFS 受损的独立预后因素。

结论

IB-IIB 期宫颈癌患者根治性子宫切除术后肿瘤中 IDO 的弥漫表达与不良临床结局相关。这些发现提示 IDO 可能是 IB-IIB 期宫颈癌术后新的预后指标。

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