Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma
Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma
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DOI：
10.7150/ijms.29995
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发表时间：
2019-05
影响因子：
3.6
通讯作者：
S. Ono;K. Nakano;Kiyofumi Takabatake;Hotaka Kawai;H. Nagatsuka
中科院分区：
文献类型：
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作者：
S. Ono;K. Nakano;Kiyofumi Takabatake;Hotaka Kawai;H. Nagatsuka
背景资料：Yes相关蛋白（雅普）是多种人类肿瘤的候选癌基因，近年来有报道称Δ Np63可增强雅普的表达及其活性。然而，雅普和Δ Np63在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）发生发展中的作用尚不清楚。因此，我们研究雅普和Δ Np63如何影响OSCC的发生和发展。研究方法：我们对整个组织样本进行免疫组化分析，以研究雅普和Δ Np63在正常口腔粘膜、上皮增生、口腔上皮异型增生（OED;低/高级别）、原位癌（CIS）和OSCC中的表达。此外，在OSCC中，我们使用Kaplan-Meier生存分析来分析临床意义。结果如下：在正常口腔粘膜和上皮增生中，雅普表达主要局限于基底层和副基底层，但雅普表达在OED、CIS和OSCC中升高。在OED中，雅普和Δ Np63的表达水平在高级别组明显高于低级别组。在OSCC组中，雅普和Δ Np63的表达模式随OSCC组织病理分化程度不同而不同。此外，雅普高表达组（其在具有强胞质染色的> 50%阳性细胞或具有核反应性的> 10%阳性细胞中显示雅普染色）显示具有较差存活率的趋势。结论：雅普和Δ Np63的表达水平与OED的严重程度相关。此外，雅普表达与OSCC生存率相关。结果提示雅普和Δ Np63的表达可作为判断OSCC发生发展的预测指标。
Background: Yes-associated protein (YAP) is a candidate oncogene in various human cancers, and recently, it has been reported that YAP expression and its activity was enhanced by ΔNp63. However, the role of YAP and ΔNp63 expression in carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has been unknown. Therefore, we investigated how YAP and ΔNp63 influence carcinogenesis and progression of OSCC. Methods: We performed immunohistochemical analyses in whole tissue samples to investigate YAP and ΔNp63 expression in normal oral mucosa, epithelial hyperplasia, oral epithelial dysplasia (OED; low/high grade), carcinoma in situ (CIS), and OSCC. Furthermore, in OSCC, we analyzed clinical significance by using Kaplan-Meier survival analysis. Results: In normal oral mucosa and epithelial hyperplasia, YAP expression was primarily confined to the basal and parabasal layers, but YAP expression was elevated in OED, CIS, and OSCC. In OED, YAP and ΔNp63 expression levels were markedly higher in high grade than in low grade. In OSCC groups, YAP and ΔNp63 expression patterns tended to differ according to histopathological differentiation of OSCC. Furthermore, the YAP high expression group, which showed YAP staining in >50% positive cells with strong cytoplasmic staining or >10% positive cells with nuclear reactivity, showed a tendency to have a poor survival rate. Conclusion: YAP and ΔNp63 expression levels correlated with grade of oral OED. Additionally, YAP expression was associated with OSCC survival rate. Our results suggested that YAP and ΔNp63 expression might serve as predictive markers to distinguish OSCC development and progression.