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血小板衍生内皮细胞生长因子作为口腔和口咽癌预后因素的可靠性。

Reliability of platelet-derived endothelial cell growth factor as a prognostic factor for oral and oropharyngeal carcinomas.

作者信息

Tsuzuki Hideaki, Sunaga Hiroshi, Ito Toshihisa, Narita Norihiko, Sugimoto Chizuru, Fujieda Shigeharu

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Fukui, Yoshida, Japan.

出版信息

Arch Otolaryngol Head Neck Surg. 2005 Dec;131(12):1071-8. doi: 10.1001/archotol.131.12.1071.

Abstract

OBJECTIVE

To identify a strong prognostic biological marker for patients with oral and oropharyngeal squamous cell carcinomas.

DESIGN

We evaluated the protein expressions of 26 tumor-associated factors, including cytokines and cytokine receptors (granulocyte colony-stimulating factor [G-CSF], interleukin 10 [IL-10], G-CSF receptor [G-CSFR], and IL-12 receptor); angiogenic factors (platelet-derived endothelial cell growth factor [PD-ECGF] and vessel count); cell cycle-related proteins (p27, cyclin D1, and cyclin E); apoptosis-related factors (wild-type p53, Bax, Bcl-2, apoptotic index, Fas, and Fas ligand); oncogene proteins (c-fos and c-Myc); cell-surface proteins (P-glycoprotein, multidrug resistance-associated protein, nm23, and CD40); intracellular proteins (aryl hydrocarbon receptor nuclear translocator, aryl hydrocarbon receptor, and heat shock protein 27); and DNA mismatch-repair genes (protein encoded by human mutL homologue 1 and the human mutS homologue of the chromosome 2p gene) by means of immunohistochemical analysis.

SETTING

Department of Otorhinolaryngology-Head and Neck Surgery, University of Fukui, Fukui, Japan.

PATIENTS

Fifty-eight patients who underwent surgical resections of oral and oropharyngeal squamous cell carcinomas.

RESULTS

A low-level PD-ECGF expression, a hypovascular count, or a low-level G-CSFR expression was associated with a favorable clinical outcome using the Kaplan-Meier method. Univariate analysis showed that PD-ECGF expression (odds, 4.19; P = .02), G-CSFR expression (odds, 4.10; P = .01), and vessel count (odds, 2.80; P = .04) had significant hazard rates. When multivariate analysis was performed on 6 factors, including sex, tumor size, lymph node metastasis, PD-ECGF expression, G-CSFR expression, and vessel count, patients with a positive expression of PD-ECGF had the highest relative risk value for death due to the disease (odds, 4.94; P = .01). Also, G-CSFR was an independent prognostic indicator in the model (odds, 3.29; P = .04). No correlations between other factors and prognoses were detected.

CONCLUSION

Expression of PD-ECGF was the most effective marker for making prognoses for oral and oropharyngeal squamous cell carcinomas, and G-CSFR expression was the second most effective among 26 tumor-associated factors.

摘要

目的

为口腔和口咽鳞状细胞癌患者确定一种强有力的预后生物学标志物。

设计

我们通过免疫组织化学分析评估了26种肿瘤相关因子的蛋白表达,这些因子包括细胞因子和细胞因子受体(粒细胞集落刺激因子[G-CSF]、白细胞介素10[IL-10]、G-CSF受体[G-CSFR]和IL-12受体);血管生成因子(血小板衍生内皮细胞生长因子[PD-ECGF]和血管计数);细胞周期相关蛋白(p27、细胞周期蛋白D1和细胞周期蛋白E);凋亡相关因子(野生型p53、Bax、Bcl-2、凋亡指数、Fas和Fas配体);癌基因蛋白(c-fos和c-Myc);细胞表面蛋白(P-糖蛋白、多药耐药相关蛋白、nm23和CD40);细胞内蛋白(芳烃受体核转运蛋白、芳烃受体和热休克蛋白27);以及DNA错配修复基因(人mutL同源物1编码的蛋白和2号染色体p基因的人mutS同源物)。

地点

日本福井县福井大学耳鼻咽喉头颈外科。

患者

58例接受口腔和口咽鳞状细胞癌手术切除的患者。

结果

采用Kaplan-Meier法分析,低水平的PD-ECGF表达、低血管计数或低水平的G-CSFR表达与良好的临床结局相关。单因素分析显示,PD-ECGF表达(比值比,4.19;P = 0.02)、G-CSFR表达(比值比,4.10;P = 0.01)和血管计数(比值比,2.80;P = 0.04)具有显著的风险率。当对包括性别、肿瘤大小、淋巴结转移、PD-ECGF表达、G-CSFR表达和血管计数在内的6个因素进行多因素分析时,PD-ECGF表达阳性的患者因疾病死亡的相对风险值最高(比值比,4.94;P = 0.01)。此外,G-CSFR是该模型中的一个独立预后指标(比值比,3.29;P = 0.04)。未检测到其他因素与预后之间的相关性。

结论

PD-ECGF表达是口腔和口咽鳞状细胞癌预后最有效的标志物,在26种肿瘤相关因子中,G-CSFR表达是第二有效的标志物。

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