Predictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia.
Predictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia.
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DOI：
10.1002/cam4.1005
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发表时间：
2017-04
期刊：
影响因子：
4
通讯作者：
Nakayama H
中科院分区：
文献类型：
--
作者：
Sakata J;Yoshida R;Matsuoka Y;Nagata M;Hirosue A;Kawahara K;Nakamura T;Nakamoto M;Hirayama M;Takahashi N;Nakashima H;Arita H;Ogi H;Hiraki A;Shinohara M;Nakayama H
口腔白斑病是一种常见的口腔潜在恶性疾病。SMAD 4最初被鉴定为肿瘤抑制因子和转化生长因子（TGF）-β信号传导的中心介导物。在这项研究中，我们的目的是确定SMAD 4在OL中的表达模式，其与炎症程度的关系，以及其作为OL恶变生物标志物的临床意义。本研究共入组150例OL患者。对从活检或切除标本中获得的石蜡包埋切片进行免疫组织化学分析。研究上皮SMAD 4表达状态、间质淋巴细胞浸润和OL恶性转化之间的关系。恶性转化与SMAD 4表达状态（P = 0.0017）和淋巴细胞浸润状态（P = 0.0054）显著相关。基于无事件生存期（EFS）的考克斯回归分析显示，SMAD 4低表达是OL患者的显著预后因素（风险比，2.632; P = 0.043）。此外，SMAD 4低表达与高淋巴细胞浸润密切相关（P = 0.00035），导致低SMAD 4表达和高淋巴细胞浸润与OL恶变之间的显著相关性（P = 0.00027）。上皮细胞SMAD 4表达和间质淋巴细胞浸润的结合可能是预测OL患者恶变的有用生物标志物。这些结果表明，不仅上皮SMAD 4的损失，而且间质的功能，可以调节恶性转化的OL的风险。
Oral leukoplakia (OL) is a common, potentially malignant disorder of the oral cavity. SMAD4 was initially identified as a tumor suppressor and central mediator of transforming growth factor (TGF)‐β signaling. In this study, we aimed to determine the expression patterns of SMAD4 in OL, its relationship with the degree of inflammation, and its clinical implications as a biomarker for OL malignant transformation. A total of 150 patients with OL were enrolled in this study. Paraffin‐embedded sections obtained from biopsy or resection specimens were subjected to immunohistochemical analysis. Associations among the status of epithelial SMAD4 expression, stromal lymphocyte infiltration, and malignant transformation of OL were examined. Malignant transformation was significantly associated with the status of SMAD4 expression (P = 0.0017) and lymphocyte infiltration status (P = 0.0054). Cox regression analysis, based on the event‐free survival (EFS), revealed that a low SMAD4 expression was a significant prognostic factor in OL patients (hazard ratio, 2.632; P = 0.043). In addition, a low SMAD4 expression was closely correlated with high lymphocyte infiltration (P = 0.00035), resulting in a significant correlation between the combination of low SMAD4 expression and high lymphocyte infiltration with malignant transformation of OL (P = 0.00027). The combination of the status of epithelial SMAD4 expression and stromal lymphocyte infiltration may be a useful biomarker for predicting malignant transformation in OL patients. These results suggest that not only epithelial SMAD4 loss, but also stromal features, may regulate the risk of malignant transformation of OL.