Ding Lei, Zhang Ziwen, Shang Duo, Cheng Jie, Yuan Hua, Wu Yunong, Song Xiaoling, Jiang Hongbing
Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, China; Institute of Stomatology, Nanjing Medical University, Nanjing, China.
J Oral Pathol Med. 2014 May;43(5):335-43. doi: 10.1111/jop.12143. Epub 2013 Dec 9.
α-Smooth muscle actin (α-SMA)-positive myofibroblasts play a pivotal role in progression and metastasis of solid carcinomas. Epithelial-mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor microenvironment are the important events in tumor metastasis. This study aimed to investigate the relationship between the expression of myofibroblasts marker, α-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC).
Immunohistochemisty was used to detect α-SMA expression in 50 OTSCCs. EMT and lymphogenesis were also identified by immunostaining with N-cadherin, vimentin, and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1).
There was a significant correlation respectively between the α-SMA (P = 0.002), vimentin (P < 0.001), N-cadherin (P = 0.025) expression and cervical lymph node metastasis of OTSCC. Carcinomas with α-SMA (P = 0.001), vimentin (P = 0.003), and N-cadherin (P = 0.012) expression were more advanced in terms of tumor-node-metastases status. Univariate analysis showed that pathologic node status (P < 0.001), α-SMA (P = 0.001), and vimentin expression (P = 0.044) was significantly associated with overall survival time, but multivariate analysis just showed the α-SMA expression (P = 0.008) and pathologic node status (P = 0.003) was independently predictive of prognosis. Furthermore, statistical analysis showed significant correlation between α-SMA expression and vimentin (P = 0.037), N-cadherin (P = 0.019), or LYVE-1 positive vessel count (P = 0.041).
Our results indicate that α-SMA-positive myofibroblasts have important impacts on cancer progression, metastasis, and survival prognosis of patients with OTSCC. The functions of α-SMA-positive myofibroblasts in OTSCC may be associated with promoting EMT of tumor cells and lymphogenesis of metastasis microenvironment.
α-平滑肌肌动蛋白(α-SMA)阳性肌成纤维细胞在实体癌的进展和转移中起关键作用。癌细胞的上皮-间质转化(EMT)和肿瘤微环境的淋巴管生成是肿瘤转移中的重要事件。本研究旨在探讨肌成纤维细胞标志物α-SMA的表达与口腔舌鳞状细胞癌(OTSCC)的临床病理特征、EMT、淋巴管生成及预后状况之间的关系。
采用免疫组织化学法检测50例OTSCC中α-SMA的表达。通过N-钙黏蛋白、波形蛋白和淋巴管内皮透明质酸受体1(LYVE-1)免疫染色鉴定EMT和淋巴管生成。
OTSCC的α-SMA(P = 0.002)、波形蛋白(P < 0.001)、N-钙黏蛋白(P = 0.025)表达与颈部淋巴结转移之间分别存在显著相关性。α-SMA(P = 0.001)、波形蛋白(P = 0.003)和N-钙黏蛋白(P = 0.012)表达的癌在肿瘤-淋巴结-转移状态方面更晚期。单因素分析显示,病理淋巴结状态(P < 0.001)、α-SMA(P = 0.001)和波形蛋白表达(P = 0.044)与总生存时间显著相关,但多因素分析仅显示α-SMA表达(P = 0.008)和病理淋巴结状态(P = 0.003)可独立预测预后。此外,统计分析显示α-SMA表达与波形蛋白(P = 0.037)、N-钙黏蛋白(P = 0.019)或LYVE-1阳性血管计数(P = 0.041)之间存在显著相关性。
我们的结果表明,α-SMA阳性肌成纤维细胞对OTSCC患者的癌症进展、转移和生存预后有重要影响。OTSCC中α-SMA阳性肌成纤维细胞的功能可能与促进肿瘤细胞的EMT和转移微环境的淋巴管生成有关。