SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.

SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.
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DOI:
10.1038/bjc.2014.500
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发表时间:
2014-11-25
影响因子:
8.8
通讯作者:
Risk JM
Risk JM
中科院分区:
医学1区
文献类型:
--
作者:
Dhanda J;Triantafyllou A;Liloglou T;Kalirai H;Lloyd B;Hanlon R;Shaw RJ;Sibson DR;Risk JM

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颈部淋巴结的囊外扩散是口腔鳞状细胞癌最重要的预后指标,但诊断必须经过组织病理学检查。原发性肿瘤中一种有前途的生物标志物--α平滑肌肌动蛋白(SMA)已被证明具有高度预后性,然而,在初步治疗之前预测ECS的经验证的生物标志物尚未可用。对102例口腔鳞癌患者的常规影像学检查与pTNM分期进行比较。从原发性肿瘤的表达微阵列中鉴定为ECS的潜在生物标志物的SERPINE 1通过mRNA表达和来自同一队列的组织微阵列上的免疫组织化学(IHC)进行验证。同样,SMA的表达也与其与ECS和生存的相关性进行了比较。分别分析肿瘤中心和前进前沿的表达;使用Kaplan-Meier生存分析确定预后能力。免疫组化结果显示SERPINE 1和SMA在肿瘤前沿的表达与ECS的发生密切相关(P<0.001)。在所有病例中,ECS与一种或两种蛋白质的表达相关。SMA+/SERPINE 1+联合表达与不良生存率高度显著相关(P<0.001)。MRI对淋巴结转移(56%)和ECS(7%)的敏感性较差。无论是单独使用还是联合使用,SERPINE 1和SMA在检测ECS方面均上级MRI(灵敏度:SERPINE 1:95% SMA:82%联合使用:81%)。SMA和SERPINE 1免疫组化的组合具有作为OSCC预后生物标志物的潜力。我们的研究结果表明,生物标志物在侵入性前沿可能是必要的预测ECS或治疗分层。
Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available. In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan–Meier survival analysis. Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95% SMA: 82% combination: 81%). A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.
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